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Review

Reprogramming the tumor microenvironment: tumor-induced immunosuppressive factors paralyze T cells

, , , &
Article: e1016700 | Received 19 Dec 2014, Accepted 03 Feb 2015, Published online: 17 Jun 2015

References

  • Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144:646-74; PMID:21376230; http://dx.doi.org/10.1016/j.cell.2011.02.013
  • Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 2012; 21:309-22; PMID:22439926; http://dx.doi.org/10.1016/j.ccr.2012.02.022
  • Palazon A, Aragones J, Morales-Kastresana A, de Landazuri MO, Melero I. Molecular pathways: hypoxia response in immune cells fighting or promoting cancer. Clin Cancer Res 2012; 18:1207-13; PMID:22205687; http://dx.doi.org/10.1158/1078-0432.CCR-11-1591
  • Lardner A. The effects of extracellular pH on immune function. J Leukoc Biol 2001; 69:522-30; PMID:11310837
  • Singer K, Kastenberger M, Gottfried E, Hammerschmied CG, Buttner M, Aigner M, Seliger B, Walter B, Schlösser H, Hartmann A, et al. Warburg phenotype in renal cell carcinoma: high expression of glucose-transporter 1 (GLUT-1) correlates with low CD8(+) T-cell infiltration in the tumor. Int J Cancer 2011; 128:2085-95; PMID:20607826; http://dx.doi.org/10.1002/ijc.25543
  • Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012; 12:252-64; PMID:22437870; http://dx.doi.org/10.1038/nrc3239
  • Karni R, Jove R, Levitzki A. Inhibition of pp60c-Src reduces Bcl-XL expression and reverses the transformed phenotype of cells overexpressing EGF and HER-2 receptors. Oncogene 1999; 18:4654-62; PMID:10467412; http://dx.doi.org/10.1038/sj.onc.1202835
  • Sa G, Das T, Moon C, Hilston CM, Rayman PA, Rini BI, Tannenbaum CS, Finke JH. GD3, an overexpressed tumor-derived ganglioside, mediates the apoptosis of activated but not resting T cells. Cancer Res 2009; 69:3095-104; PMID:19276353; http://dx.doi.org/10.1158/0008-5472.CAN-08-3776
  • Bronte V, Zanovello P. Regulation of immune responses by L-arginine metabolism. Nat Rev Immunol 2005; 5:641-54; PMID:16056256; http://dx.doi.org/10.1038/nri1668
  • Igney FH, Krammer PH. Tumor counterattack: fact or fiction? Cancer Immunol Immunother 2005; 54:1127-36; PMID:15889255; http://dx.doi.org/10.1007/s00262-005-0680-7
  • Leone P, Shin EC, Perosa F, Vacca A, Dammacco F, Racanelli V. MHC class I antigen processing and presenting machinery: organization, function, and defects in tumor cells. J Natl Cancer Inst 2013; 105:1172-87; PMID:23852952; http://dx.doi.org/10.1093/jnci/djt184
  • Campoli M, Ferrone S. HLA antigen changes in malignant cells: epigenetic mechanisms and biologic significance. Oncogene 2008; 27:5869-85; PMID:18836468; http://dx.doi.org/10.1038/onc.2008.273
  • Garrido F, Algarra I. MHC antigens and tumor escape from immune surveillance. Adv Cancer Res 2001; 83:117-58; PMID:11665717; http://dx.doi.org/10.1016/S0065-230X(01)83005-0
  • Garcia‐Lora A, Algarra I, Garrido F. MHC class I antigens, immune surveillance, and tumor immune escape. J Cell Physiol 2003; 195:346-55; PMID:12704644; http://dx.doi.org/10.1002/jcp.10290
  • Romero JM, Jimenez P, Cabrera T, Cozar JM, Pedrinaci S, Tallada M, Garrido F, Ruiz-Cabello F. Coordinated downregulation of the antigen presentation machinery and HLA class I/beta2-microglobulin complex is responsible for HLA-ABC loss in bladder cancer. Int J Cancer 2005; 113:605-10; PMID:15455355; http://dx.doi.org/10.1002/ijc.20499
  • Dierssen JW, de Miranda NF, Ferrone S, van Puijenbroek M, Cornelisse CJ, Fleuren GJ, van Wezel T, Morreau H. HNPCC versus sporadic microsatellite-unstable colon cancers follow different routes toward loss of HLA class I expression. BMC Cancer 2007; 7:33; PMID:17316446; http://dx.doi.org/10.1186/1471-2407-7-33
  • de Miranda NF, Nielsen M, Pereira D, van Puijenbroek M, Vasen HF, Hes FJ, van Wezel T, Morreau H. MUTYH-associated polyposis carcinomas frequently lose HLA class I expression - a common event amongst DNA-repair-deficient colorectal cancers. J Pathol 2009; 219:69-76; PMID:19462419; http://dx.doi.org/10.1002/path.2569
  • Bicknell DC, Kaklamanis L, Hampson R, Bodmer WF, Karran P. Selection for beta 2-microglobulin mutation in mismatch repair-defective colorectal carcinomas. Curr Biol 1996; 6:1695-7; PMID:8994836; http://dx.doi.org/10.1016/S0960-9822(02)70795-1
  • Bennaceur K, Chapman JA, Touraine JL, Portoukalian J. Immunosuppressive networks in the tumour environment and their effect in dendritic cells. Biochim Biophys Acta 2009; 1795:16-24; PMID:18675885
  • Seliger B, Hohne A, Knuth A, Bernhard H, Ehring B, Tampe R, Huber C. Reduced membrane major histocompatibility complex class I density and stability in a subset of human renal cell carcinomas with low TAP and LMP expression. Clin Cancer Res 1996; 2:1427-33; PMID:9816317
  • Seliger B, Maeurer MJ, Ferrone S. Antigen-processing machinery breakdown and tumor growth. Immunol Today 2000; 21:455-64; PMID:10953098; http://dx.doi.org/10.1016/S0167-5699(00)01692-3
  • Belicha-Villanueva A. Regulation of Classical and Non-classical Major Histocompatibility Complex Class I Molecules. ProQuest 2008
  • Bai X-F, Liu J, Li O, Zheng P, Liu Y. Antigenic drift as a mechanism for tumor evasion of destruction by cytolytic T lymphocytes. J Clin Invest 2003; 111:1487-96; PMID:12750398; http://dx.doi.org/10.1172/JCI17656
  • Seliger B, Wollscheid U, Momburg F, Blankenstein T, Huber C. Coordinate downregulation of multiple MHC class I antigen processing genes in chemical‐induced murine tumor cell lines of distinct origin. Tissue Antigens 2000; 56:327-36; PMID:11098932; http://dx.doi.org/10.1034/j.1399-0039.2000.560404.x
  • Ullrich E, Koch J, Cerwenka A, Steinle A. New prospects on the NKG2D/NKG2DL system for oncology. Oncoimmunology 2013; 2:e26097; PMID:24353908; http://dx.doi.org/10.4161/onci.26097
  • Groh V, Wu J, Yee C, Spies T. Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature 2002; 419:734-8; PMID:12384702; http://dx.doi.org/10.1038/nature01112
  • Raulet DH, Gasser S, Gowen BG, Deng W, Jung H. Regulation of ligands for the NKG2D activating receptor. Annu Rev Immunol 2013; 31:413-41; PMID:23298206; http://dx.doi.org/10.1146/annurev-immunol-032712-095951
  • Jinushi M, Vanneman M, Munshi NC, Tai YT, Prabhala RH, Ritz J, Neuberg D, Anderson KC, Carrasco DR, Dranoff G. MHC class I chain-related protein A antibodies and shedding are associated with the progression of multiple myeloma. Proc Natl Acad Sci U S A 2008; 105:1285-90; PMID:18202175; http://dx.doi.org/10.1073/pnas.0711293105
  • Marten A, von Lilienfeld-Toal M, Buchler MW, Schmidt J. Soluble MIC is elevated in the serum of patients with pancreatic carcinoma diminishing gammadelta T cell cytotoxicity. Int J Cancer 2006; 119:2359-65; PMID:16929491; http://dx.doi.org/10.1002/ijc.22186
  • Salih HR, Goehlsdorf D, Steinle A. Release of MICB molecules by tumor cells: mechanism and soluble MICB in sera of cancer patients. Hum Immunol 2006; 67:188-95; PMID:16698441; http://dx.doi.org/10.1016/j.humimm.2006.02.008
  • Waldhauer I, Goehlsdorf D, Gieseke F, Weinschenk T, Wittenbrink M, Ludwig A, Stevanovic S, Rammensee HG, Steinle A. Tumor-associated MICA is shed by ADAM proteases. Cancer Res 2008; 68:6368-76; PMID:18676862; http://dx.doi.org/10.1158/0008-5472.CAN-07-6768
  • Salih HR, Rammensee HG, Steinle A. Cutting Edge: Down-Regulation of MICA on Human Tumors by Proteolytic Shedding. J Immunol 2002; 169:4098-102; PMID:12370336; http://dx.doi.org/10.4049/jimmunol.169.8.4098
  • Clayton A, Mitchell JP, Linnane S, Mason MD, Tabi Z. Human tumor-derived exosomes down-modulate NKG2D expression. J Immunol 2008; 180:7249-58; PMID:18490724; http://dx.doi.org/10.4049/jimmunol.180.11.7249
  • Fernández-Messina L, Ashiru O, Boutet P, Agüera-González S, Skepper JN, Reyburn HT, Valés-Gómez M. Differential mechanisms of shedding of the glycosylphosphatidylinositol (GPI)-anchored NKG2D ligands. J Biol Chem 2010; 285:8543-51; http://dx.doi.org/10.1074/jbc.M109.045906
  • Waldhauer I, Steinle A. Proteolytic release of soluble UL16-binding protein 2 from tumor cells. Cancer Res 2006; 66:2520-6; PMID:16510567; http://dx.doi.org/10.1158/0008-5472.CAN-05-2520
  • Wu J, Song Y, Bakker AB, Bauer S, Spies T, Lanier LL, et al. An activating immunoreceptor complex formed by NKG2D and DAP10. Science 1999; 285:730-2; PMID:10426994; http://dx.doi.org/10.1126/science.285.5428.730
  • Raffaghello L, Prigione I, Airoldi I, Camoriano M, Levreri I, Gambini C, Pende D, Steinle A, Ferrone S, Pistoia V. Downregulation and/or release of NKG2D ligands as immune evasion strategy of human neuroblastoma. Neoplasia 2004; 6:558-68; PMID:15548365; http://dx.doi.org/10.1593/neo.04316
  • Huergo-Zapico L, Acebes-Huerta A, Lopez-Soto A, Villa-Alvarez M, Gonzalez-Rodriguez AP, Gonzalez S. Molecular Bases for the Regulation of NKG2D Ligands in Cancer. Front Immunol 2014; 5:106; PMID:24711808; http://dx.doi.org/10.3389/fimmu.2014.00106
  • Groth A, Klöss S, Pogge von Strandmann E, Koehl U, Koch J. Mechanisms of tumor and viral immune escape from natural killer cell-mediated surveillance. J Innate Immun 2011; 3:344-54; PMID:21576922; http://dx.doi.org/10.1159/000327014
  • Hellebrekers DM, Castermans K, Vire E, Dings RP, Hoebers NT, Mayo KH, Oude Egbrink MG, Molema G, Fuks F, van Engeland M, et al. Epigenetic regulation of tumor endothelial cell anergy: silencing of intercellular adhesion molecule-1 by histone modifications. Cancer Res 2006; 66:10770-7; PMID:17108113; http://dx.doi.org/10.1158/0008-5472.CAN-06-1609
  • Piali L, Fichtel A, Terpe HJ, Imhof BA, Gisler RH. Endothelial vascular cell adhesion molecule 1 expression is suppressed by melanoma and carcinoma. J Exp Med 1995; 181:811-6; PMID:7530765; http://dx.doi.org/10.1084/jem.181.2.811
  • Wu T. The role of vascular cell adhesion molecule-1 in tumor immune evasion. Cancer Res 2007; 67:6003-6; PMID:17616653; http://dx.doi.org/10.1158/0008-5472.CAN-07-1543
  • Rose DM, Grabovsky V, Alon R, Ginsberg MH. The Affinity of Integrin 4 1 Governs Lymphocyte Migration. J Immunol 2001; 167:2824-30; PMID:11509628; http://dx.doi.org/10.4049/jimmunol.167.5.2824
  • Rose DM, Han J, Ginsberg MH. α4 integrins and the immune response. Immunol Rev 2002; 186:118-24; PMID:12234367; http://dx.doi.org/10.1034/j.1600-065X.2002.18611.x
  • Schlesinger M, Bendas G. Vascular cell adhesion molecule‐1 (VCAM‐1)—An increasing insight into its role in tumorigenicity and metastasis. Int J Cancer 2014
  • Lin KY, Lu D, Hung CF, Peng S, Huang L, Jie C, Murillo F, Rowley J, Tsai YC, He L, et al. Ectopic expression of vascular cell adhesion molecule-1 as a new mechanism for tumor immune evasion. Cancer Res 2007; 67:1832-41; PMID:17308126; http://dx.doi.org/10.1158/0008-5472.CAN-06-3014
  • Hemmerlein B, Scherbening J, Kugler A, Radzun HJ. Expression of VCAM‐1, ICAM‐1, E‐and P‐selectin and tumour‐associated macrophages in renal cell carcinoma. Histopathology 2000; 37:78-83; PMID:10931222; http://dx.doi.org/10.1046/j.1365-2559.2000.00933.x
  • Vasselli JR, Shih JH, Iyengar SR, Maranchie J, Riss J, Worrell R, Torres-Cabala C, Tabios R, Mariotti A, Stearman R, et al. Predicting survival in patients with metastatic kidney cancer by gene-expression profiling in the primary tumor. Pro Natl Acad Sci 2003; 100:6958-63; http://dx.doi.org/10.1073/pnas.1131754100
  • Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, Parmentier N, Boon T, Van den Eynde BJ. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med 2003; 9:1269-74; PMID:14502282; http://dx.doi.org/10.1038/nm934
  • Wainwright DA, Balyasnikova IV, Chang AL, Ahmed AU, Moon K-S, Auffinger B, Tobias AL, Han Y, Lesniak MS. IDO expression in brain tumors increases the recruitment of regulatory T cells and negatively impacts survival. Clin Cancer Res 2012; 18:6110-21; PMID:22932670; http://dx.doi.org/10.1158/1078-0432.CCR-12-2130
  • Astigiano S, Morandi B, Costa R, Mastracci L, D'Agostino A, Ratto GB, Melioli G, Frumento G. Eosinophil granulocytes account for indoleamine 2, 3-dioxygenase-mediated immune escape in human non small cell lung cancer. Neoplasia 2005; 7:390-6; PMID:15967116; http://dx.doi.org/10.1593/neo.04658
  • Okamoto A, Nikaido T, Ochiai K, Takakura S, Saito M, Aoki Y, Ishii N, Yanaihara N, Yamada K, Takikawa O, et al. Indoleamine 2, 3-dioxygenase serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells. Clin Cancer Res 2005; 11:6030-9; PMID:16115948; http://dx.doi.org/10.1158/1078-0432.CCR-04-2671
  • Brandacher G, Perathoner A, Ladurner R, Schneeberger S, Obrist P, Winkler C, Werner ER, Werner-Felmayer G, Weiss HG, Göbel G, et al. Prognostic value of indoleamine 2, 3-dioxygenase expression in colorectal cancer: effect on tumor-infiltrating T cells. Clin Cancer Res 2006; 12:1144-51; PMID:16489067; http://dx.doi.org/10.1158/1078-0432.CCR-05-1966
  • Pan K, Wang H, Chen M-s, Zhang H-k, Weng D-s, Zhou J, Huang W, Li JJ, Song HF, Xia JC. Expression and prognosis role of indoleamine 2, 3-dioxygenase in hepatocellular carcinoma. J Cancer Res Clin Oncol 2008; 134:1247-53; PMID:18438685; http://dx.doi.org/10.1007/s00432-008-0395-1
  • Godin-Ethier J, Hanafi L-A, Piccirillo CA, Lapointe R. Indoleamine 2, 3-dioxygenase expression in human cancers: clinical and immunologic perspectives. Clin Cancer Res 2011; 17:6985-91; PMID:22068654; http://dx.doi.org/10.1158/1078-0432.CCR-11-1331
  • Harden JL, Egilmez NK. Indoleamine 2,3-dioxygenase and dendritic cell tolerogenicity. Immunol Invest 2012; 41:738-64; PMID:23017144; http://dx.doi.org/10.3109/08820139.2012.676122
  • Munn DH, Shafizadeh E, Attwood JT, Bondarev I, Pashine A, Mellor AL. Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med 1999; 189:1363-72; PMID:10224276; http://dx.doi.org/10.1084/jem.189.9.1363
  • Fallarino F, Grohmann U, You S, McGrath BC, Cavener DR, Vacca C, Orabona C, Bianchi R, Belladonna ML, Volpi C, et al. The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J Immunol 2006; 176:6752-61; PMID:16709834; http://dx.doi.org/10.4049/jimmunol.176.11.6752
  • Frumento G, Rotondo R, Tonetti M, Damonte G, Benatti U, Ferrara GB. Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase. J Exp Med 2002; 196:459-68; PMID:12186838; http://dx.doi.org/10.1084/jem.20020121
  • Platten M, Wick W, Van den Eynde BJ. Tryptophan catabolism in cancer: beyond IDO and tryptophan depletion. Cancer Res 2012; 72:5435-40; PMID:23090118; http://dx.doi.org/10.1158/0008-5472.CAN-12-0569
  • Fallarino F, Grohmann U, Vacca C, Bianchi R, Orabona C, Spreca A, Fioretti MC, Puccetti P. T cell apoptosis by tryptophan catabolism. Cell Death Differ 2002; 9:1069-77; PMID:12232795; http://dx.doi.org/10.1038/sj.cdd.4401073
  • Munn DH, Mellor AL. IDO and tolerance to tumors. Trends Mol Med 2004; 10:15-8; PMID:14720581; http://dx.doi.org/10.1016/j.molmed.2003.11.003
  • Terness P, Bauer TM, Röse L, Dufter C, Watzlik A, Simon H, Opelz G. Inhibition of Allogeneic T Cell Proliferation by Indoleamine 2, 3-Dioxygenase-expressing Dendritic Cells Mediation of Suppression by Tryptophan Metabolites. J Exp Med 2002; 196:447-57; PMID:12186837; http://dx.doi.org/10.1084/jem.20020052
  • Zoso A, Mazza EM, Bicciato S, Mandruzzato S, Bronte V, Serafini P, Inverardi L. Human fibrocytic myeloid-derived suppressor cells express IDO and promote tolerance via Treg-cell expansion. Eur J Immunol 2014; PMID:25113564
  • Muller AJ, DuHadaway JB, Donover PS, Sutanto-Ward E, Prendergast GC. Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat Med 2005; 11:312-9; PMID:15711557; http://dx.doi.org/10.1038/nm1196
  • Löb S, Königsrainer A, Rammensee H-G, Opelz G, Terness P. Inhibitors of indoleamine-2, 3-dioxygenase for cancer therapy: can we see the wood for the trees? Nat Rev Cancer 2009; 9:445-52; PMID:19461669; http://dx.doi.org/10.1038/nrc2639
  • Katz JB, Muller AJ, Prendergast GC. Indoleamine 2,3-dioxygenase in T-cell tolerance and tumoral immune escape. Immunol Rev 2008; 222:206-21; PMID:18364004; http://dx.doi.org/10.1111/j.1600-065X.2008.00610.x
  • Qian F, Villella J, Wallace PK, Mhawech-Fauceglia P, Tario JD, Andrews C, Matsuzaki J, Valmori D, Ayyoub M, Frederick PJ, et al. Efficacy of levo-1-methyl tryptophan and dextro-1-methyl tryptophan in reversing indoleamine-2, 3-dioxygenase-mediated arrest of T-Cell proliferation in human epithelial ovarian cancer. Cancer Res 2009; 69:5498-504; PMID:19491279; http://dx.doi.org/10.1158/0008-5472.CAN-08-2106
  • Suzuki S, Tone S, Takikawa O, Kubo T, Kohno I, Minatogawa Y. Expression of indoleamine 2, 3-dioxygenase and tryptophan 2, 3-dioxygenase in early concepti. Biochem J 2001; 355:425-9; PMID:11284730; http://dx.doi.org/10.1042/0264-6021:3550425
  • Soliman H, Mediavilla-Varela M, Antonia S. Indoleamine 2, 3-dioxygenase: is it an immune suppressor? Cancer J (Sudbury, Mass) 2010; 16; PMID:20693847
  • Wu G, MORRIS JS. Arginine metabolism: nitric oxide and beyond. Biochem J 1998; 336:1-17; PMID:9806879
  • de Boniface J, Mao Y, Schmidt-Mende J, Kiessling R, Poschke I. Expression patterns of the immunomodulatory enzyme arginase 1 in blood, lymph nodes and tumor tissue of early-stage breast cancer patients. Oncoimmunology 2012; 1:1305; PMID:23243594; http://dx.doi.org/10.4161/onci.21678
  • Rodriguez PC, Ernstoff MS, Hernandez C, Atkins M, Zabaleta J, Sierra R, Ochoa AC. Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res 2009; 69:1553-60; PMID:19201693; http://dx.doi.org/10.1158/0008-5472.CAN-08-1921
  • Zea AH, Rodriguez PC, Atkins MB, Hernandez C, Signoretti S, Zabaleta J, McDermott D, Quiceno D, Youmans A, O'Neill A, et al. Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res 2005; 65:3044-8; PMID:15833831
  • Vanderstraeten A, Luyten C, Verbist G, Tuyaerts S, Amant F. Mapping the immunosuppressive environment in uterine tumors: implications for immunotherapy. Cancer Immunol, Immunother 2014; 63:545-57; http://dx.doi.org/10.1007/s00262-014-1537-8
  • Mumenthaler SM, Yu H, Tze S, Cederbaum SD, Pegg AE, Seligson DB, Grody WW. Expression of arginase II in prostate cancer. Int J Oncol 2008; 32:357-65; PMID:18202758
  • Huang B, Lei Z, Zhao J, Gong W, Liu J, Chen Z, Liu Y, Li D, Yuan Y, Zhang GM, et al. CCL2/CCR2 pathway mediates recruitment of myeloid suppressor cells to cancers. Cancer Lett 2007; 252:86-92; PMID:17257744; http://dx.doi.org/10.1016/j.canlet.2006.12.012
  • Umansky V, Sevko A. Tumor microenvironment and myeloid-derived suppressor cells. Cancer Microenviron 2013; 6:169-77; PMID:23242672; http://dx.doi.org/10.1007/s12307-012-0126-7
  • Raber P, Ochoa AC, Rodríguez PC. Metabolism of L-arginine by myeloid-derived suppressor cells in cancer: mechanisms of T cell suppression and therapeutic perspectives. Immunol Invest 2012; 41:614-34; PMID:23017138; http://dx.doi.org/10.3109/08820139.2012.680634
  • Rodriguez PC, Quiceno DG, Zabaleta J, Ortiz B, Zea AH, Piazuelo MB, Delgado A, Correa P, Brayer J, Sotomayor EM, et al. Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res 2004; 64:5839-49; PMID:15313928; http://dx.doi.org/10.1158/0008-5472.CAN-04-0465
  • Munder M. Arginase: an emerging key player in the mammalian immune system. British J Pharmacol 2009; 158:638-51; PMID:19764983; http://dx.doi.org/10.1111/j.1476-5381.2009.00291.x
  • Rodriguez PC, Quiceno DG, Ochoa AC. L-arginine availability regulates T-lymphocyte cell-cycle progression. Blood 2007; 109:1568-73; PMID:17023580; http://dx.doi.org/10.1182/blood-2006-06-031856
  • Pervin S, Singh R, Chaudhuri G. Nitric oxide-induced cytostasis and cell cycle arrest of a human breast cancer cell line (MDA-MB-231): potential role of cyclin D1. Proc Natl Acad Sci 2001; 98:3583-8; http://dx.doi.org/10.1073/pnas.041603998
  • Kostourou V, Cartwright J, Johnstone A, Boult J, Cullis E, Whitley G, Robinson SP. The role of tumour-derived iNOS in tumour progression and angiogenesis. British J Cancer 2010; 104:83-90; PMID:21139581; http://dx.doi.org/10.1038/sj.bjc.6606034
  • Mazzoni A, Bronte V, Visintin A, Spitzer JH, Apolloni E, Serafini P, Zanovello P, Segal DM. Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism. J Immunol 2002; 168:689-95; PMID:11777962; http://dx.doi.org/10.4049/jimmunol.168.2.689
  • Blesson S, Thiery J, Gaudin C, Stancou R, Kolb JP, Moreau JL, Theze J, Mami-Chouaib F, Chouaib S. Analysis of the mechanisms of human cytotoxic T lymphocyte response inhibition by NO. Int Immunol 2002; 14:1169-78; PMID:12356682; http://dx.doi.org/10.1093/intimm/dxf081
  • Munder M, Schneider H, Luckner C, Giese T, Langhans C-D, Fuentes JM, Kropf P, Mueller I, Kolb A, Modolell M, et al. Suppression of T-cell functions by human granulocyte arginase. Blood 2006; 108:1627-34
  • Tenu J-P, Lepoivre M, Moali C, Brollo M, Mansuy D, Boucher J-L. Effects of the New Arginase Inhibitor N ω-Hydroxy-nor-l-Arginine on NO Synthase Activity in Murine Macrophages. Nitric Oxide 1999; 3:427-38; PMID:10637120; http://dx.doi.org/10.1006/niox.1999.0255
  • Kitayama J, Emoto S, Yamaguchi H, Ishigami H, Yamashita H, Seto Y, Matsuzaki K, Watanabe T. CD90 (+) CD45 (−) intraperitoneal mesothelial-like cells inhibit T cell activation by production of arginase I. Cell Immunol 2014; 288:8-14; PMID:24556645; http://dx.doi.org/10.1016/j.cellimm.2014.01.008
  • Wang R. Innate immune regulation and cancer immunotherapy. Springer, 2012.
  • Zhu X, Pribis JP, Rodriguez PC, Morris Jr SM, Vodovotz Y, Billiar TR, Ochoa JB. The central role of arginine catabolism in T-cell dysfunction and increased susceptibility to infection after physical injury. Ann Surg 2014; 259:171-8; PMID:23470573; http://dx.doi.org/10.1097/SLA.0b013e31828611f8
  • Kusmartsev SA, Li Y, Chen S-H. Gr-1+ myeloid cells derived from tumor-bearing mice inhibit primary T cell activation induced through CD3/CD28 costimulation. J Immunol 2000; 165:779-85; PMID:10878351; http://dx.doi.org/10.4049/jimmunol.165.2.779
  • Zhou R, He PL, Ren YX, Wang WH, Zhou RY, Wan H, Ono S, Fujiwara H, Zuo JP. Myeloid suppressor cell‐associated immune dysfunction in CSA1M fibrosarcoma tumor‐bearing mice. Cancer Sci 2007; 98:882-9; PMID:17433038; http://dx.doi.org/10.1111/j.1349-7006.2007.00465.x
  • Serafini P, Meckel K, Kelso M, Noonan K, Califano J, Koch W, Dolcetti L, Bronte V, Borrello I. Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J Exp Med 2006; 203:2691-702; PMID:17101732; http://dx.doi.org/10.1084/jem.20061104
  • Ibiza S, Serrador J. The role of nitric oxide in the regulation of adaptive immune responses. Inmunología 2008; 27:103-17
  • Sosroseno W, Herminajeng E, Bird P, Seymour G. l‐arginine‐dependent nitric oxide production of a murine macrophage‐like RAW 264.7 cell line stimulated with Porphyromonas gingivalis lipopolysaccharide. Oral Microbiol Immunol 2004; 19:65-70; PMID:14871343; http://dx.doi.org/10.1046/j.0902-0055.2003.00108.x
  • Spiegel S, Merrill AH, Jr. Sphingolipid metabolism and cell growth regulation. Faseb J 1996; 10:1388-97; PMID:8903509
  • Krengel U, Bousquet PA. Molecular recognition of gangliosides and their potential for cancer immunotherapies. Front Immunol 2014; 5:325; PMID:25101077; http://dx.doi.org/10.3389/fimmu.2014.00325
  • McKallip R, Li R, Ladisch S. Tumor gangliosides inhibit the tumor-specific immune response. J Immunol 1999; 163:3718-26; PMID:10490967
  • Li R, Villacreses N, Ladisch S. Human tumor gangliosides inhibit murine immune responses in vivo. Cancer Res 1995; 55:211-4; PMID:7812945
  • Biswas S, Biswas K, Richmond A, Ko J, Ghosh S, Simmons M, Rayman P, Rini B, Gill I, Tannenbaum CS, et al. Elevated levels of select gangliosides in T cells from renal cell carcinoma patients is associated with T cell dysfunction. J Immunol 2009; 183:5050-8; PMID:19801523; http://dx.doi.org/10.4049/jimmunol.0900259
  • Das T, Sa G, Paszkiewicz-Kozik E, Hilston C, Molto L, Rayman P, Kudo D, Biswas K, Bukowski RM, Finke JH, et al. Renal cell carcinoma tumors induce T cell apoptosis through receptor-dependent and receptor-independent pathways. J Immunol 2008; 180:4687-96; PMID:18354192; http://dx.doi.org/10.4049/jimmunol.180.7.4687
  • Raval G, Biswas S, Rayman P, Biswas K, Sa G, Ghosh S, Thornton M, Hilston C, Das T, Bukowski R, et al. TNF-alpha induction of GM2 expression on renal cell carcinomas promotes T cell dysfunction. J Immunol 2007; 178:6642-52; PMID:17475896; http://dx.doi.org/10.4049/jimmunol.178.10.6642
  • Uzzo RG, Rayman P, Kolenko V, Clark PE, Cathcart MK, Bloom T, Novick AC, Bukowski RM, Hamilton T, Finke JH. Renal cell carcinoma-derived gangliosides suppress nuclear factor-kappaB activation in T cells. J Clin Invest 1999; 104:769-76; PMID:10491412; http://dx.doi.org/10.1172/JCI6775
  • Rayman P, Wesa AK, Richmond AL, Das T, Biswas K, Raval G, Storkus WJ, Tannenbaum C, Novick A, Bukowski R, et al. Effect of renal cell carcinomas on the development of type 1 T-cell responses. Clin Cancer Res 2004; 10:6360S-6S; PMID:15448031; http://dx.doi.org/10.1158/1078-0432.CCR-050011
  • Biswas K, Richmond A, Rayman P, Biswas S, Thornton M, Sa G, Das T, Zhang R, Chahlavi A, Tannenbaum CS, et al. GM2 expression in renal cell carcinoma: potential role in tumor-induced T-cell dysfunction. Cancer Res 2006; 66:6816-25; PMID:16818659; http://dx.doi.org/10.1158/0008-5472.CAN-06-0250
  • Crespo FA, Sun X, Cripps JG, Fernandez-Botran R. The immunoregulatory effects of gangliosides involve immune deviation favoring type-2 T cell responses. J Leukoc Biol 2006; 79:586-95; PMID:16415169; http://dx.doi.org/10.1189/jlb.0705395
  • Caldwell S, Heitger A, Shen W, Liu Y, Taylor B, Ladisch S. Mechanisms of ganglioside inhibition of APC function. J Immunol 2003; 171:1676-83; PMID:12902465; http://dx.doi.org/10.4049/jimmunol.171.4.1676
  • Thornton MV, Kudo D, Rayman P, Horton C, Molto L, Cathcart MK, Ng C, Paszkiewicz-Kozik E, Bukowski R, Derweesh I, et al. Degradation of NF-kappa B in T cells by gangliosides expressed on renal cell carcinomas. J Immunol 2004; 172:3480-90; PMID:15004148; http://dx.doi.org/10.4049/jimmunol.172.6.3480
  • Lee HC, Wondimu A, Liu Y, Ma JS, Radoja S, Ladisch S. Ganglioside inhibition of CD8+ T cell cytotoxicity: interference with lytic granule trafficking and exocytosis. J Immunol 2012; 189:3521-7; PMID:22956583; http://dx.doi.org/10.4049/jimmunol.1201256
  • Retter MW, Johnson JC, Peckham DW, Bannink JE, Bangur CS, Dresser K, Cai F, Foy TM, Fanger NA, Fanger GR, et al. Characterization of a proapoptotic antiganglioside GM2 monoclonal antibody and evaluation of its therapeutic effect on melanoma and small cell lung carcinoma xenografts. Cancer Res 2005; 65:6425-34; PMID:16024647; http://dx.doi.org/10.1158/0008-5472.CAN-05-0300
  • Lloyd KO, Gordon CM, Thampoe IJ, DiBenedetto C. Cell surface accessibility of individual gangliosides in malignant melanoma cells to antibodies is influenced by the total ganglioside composition of the cells. Cancer Res 1992; 52:4948-53; PMID:1516051
  • Mazorra Z, Mesa C, Fernández LE. GM3 ganglioside: a novel target for the therapy against melanoma. Biotecnología Aplicada 2009; 26:256-9
  • Houghton AN, Mintzer D, Cordon-Cardo C, Welt S, Fliegel B, Vadhan S, Carswell E, Melamed MR, Oettgen HF, Old LJ. Mouse monoclonal IgG3 antibody detecting GD3 ganglioside: a phase I trial in patients with malignant melanoma. Proc Natl Acad Sci U S A 1985; 82:1242-6; PMID:3883355; http://dx.doi.org/10.1073/pnas.82.4.1242
  • Cheung NK, Neely JE, Landmeier B, Nelson D, Miraldi F. Targeting of ganglioside GD2 monoclonal antibody to neuroblastoma. J Nucl Med 1987; 28:1577-83; PMID:3655911
  • Ahmed M, Cheung N-KV. Engineering anti-GD2 monoclonal antibodies for cancer immunotherapy. FEBS Lett 588:288-97; PMID:24295643
  • Fernandez LE, Gabri MR, Guthmann MD, Gomez RE, Gold S, Fainboim L, Gomez DE, Alonso DF. NGcGM3 ganglioside: a privileged target for cancer vaccines. J Immunol Res 2010; 2010:814397
  • Groux H, Bigler M, de Vries JE, Roncarolo M-G. Inhibitory and stimulatory effects of IL-10 on human CD8+ T cells. J Immunol 1998; 160:3188-93; PMID:9531274
  • Mocellin S, Marincola FM, Young HA. Interleukin-10 and the immune response against cancer: a counterpoint. J Leukocyte Biol 2005; 78:1043-51; PMID:16204623; http://dx.doi.org/10.1189/jlb.0705358
  • Kim J, Modlin RL, Moy RL, Dubinett SM, McHugh T, Nickoloff BJ, Uyemura K. IL-10 production in cutaneous basal and squamous cell carcinomas. A mechanism for evading the local T cell immune response. J Immunol 1995; 155:2240-7; PMID:7636270
  • Huang M, Wang J, Lee P, Sharma S, Mao JT, Meissner H, Uyemura K, Modlin R, Wollman J, Dubinett SM. Human non-small cell lung cancer cells express a type 2 cytokine pattern. Cancer Res 1995; 55:3847-53; PMID:7641203
  • Knoefel B, Nuske K, Steiner T, Junker K, Kosmehl H, Rebstock K, Reinhold D, Junker U. Renal cell carcinomas produce IL-6, IL-10, IL-11, and TGF-beta 1 in primary cultures and modulate T lymphocyte blast transformation. J Interferon Cytokine Res 1997; 17:95-102; PMID:9058315; http://dx.doi.org/10.1089/jir.1997.17.95
  • Venetsanakos E, Beckman I, Bradley J, Skinner JM. High incidence of interleukin 10 mRNA but not interleukin 2 mRNA detected in human breast tumours. Br J Cancer 1997; 75:1826-30; PMID:9192989; http://dx.doi.org/10.1038/bjc.1997.311
  • Pisa P, Halapi E, Pisa EK, Gerdin E, Hising C, Bucht A, Gerdin B, Kiessling R. Selective expression of interleukin 10, interferon gamma, and granulocyte-macrophage colony-stimulating factor in ovarian cancer biopsies. Proc Natl Acad Sci U S A 1992; 89:7708-12; PMID:1502188; http://dx.doi.org/10.1073/pnas.89.16.7708
  • Bolpetti A, Silva JS, Villa LL, Lepique AP. Interleukin-10 production by tumor infiltrating macrophages plays a role in Human Papillomavirus 16 tumor growth. BMC Immunol 2010; 11:27; PMID:20525400; http://dx.doi.org/10.1186/1471-2172-11-27
  • Yue FY, Dummer R, Geertsen R, Hofbauer G, Laine E, Manolio S, Burg G. Interleukin-10 is a growth factor for human melanoma cells and down-regulates HLA class-I, HLA class-II and ICAM-1 molecules. Int J Cancer 1997; 71:630-7; PMID:9178819; http://dx.doi.org/10.1002/(SICI)1097-0215(19970516)71:4%3c630::AID-IJC20%3e3.0.CO;2-E
  • Fujieda S, Sunaga H, Tsuzuki H, Fan GK, Saito H. IL-10 expression is associated with the expression of platelet-derived endothelial cell growth factor and prognosis in oral and oropharyngeal carcinoma. Cancer Lett 1999; 136:1-9; PMID:10211932; http://dx.doi.org/10.1016/S0304-3835(98)00281-X
  • Sher A, Fiorentino D, Caspar P, Pearce E, Mosmann T. Production of IL-10 by CD4+ T lymphocytes correlates with down-regulation of Th1 cytokine synthesis in helminth infection. J Immunol 1991; 147:2713-6; PMID:1680917
  • de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 1991; 174:1209-20; PMID:1940799; http://dx.doi.org/10.1084/jem.174.5.1209
  • Taylor A, Verhagen J, Blaser K, Akdis M, Akdis CA. Mechanisms of immune suppression by interleukin‐10 and transforming growth factor‐β: the role of T regulatory cells. Immunology 2006; 117:433-42; PMID:16556256; http://dx.doi.org/10.1111/j.1365-2567.2006.02321.x
  • Steinman RM, Hawiger D, Nussenzweig MC. Tolerogenic dendritic cells. Annu Rev Immunol 2003; 21:685-711; PMID:12615891; http://dx.doi.org/10.1146/annurev.immunol.21.120601.141040
  • Nabarro S, Himoudi N, Papanastasiou A, Gilmour K, Gibson S, Sebire N, Thrasher A, Blundell MP, Hubank M, Canderan G, et al. Coordinated oncogenic transformation and inhibition of host immune responses by the PAX3-FKHR fusion oncoprotein. J Exp Med 2005; 202:1399-410; PMID:16287709; http://dx.doi.org/10.1084/jem.20050730
  • Wang T, Niu G, Kortylewski M, Burdelya L, Shain K, Zhang S, Bhattacharya R, Gabrilovich D, Heller R, Coppola D, et al. Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nat Med 2004; 10:48-54; PMID:14702634; http://dx.doi.org/10.1038/nm976
  • Sevko A, Umansky V. Myeloid-derived suppressor cells interact with tumors in terms of myelopoiesis, tumorigenesis and immunosuppression: thick as thieves. J Cancer 2013; 4:3-11; PMID:23386900; http://dx.doi.org/10.7150/jca.5047
  • Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 2009; 9:162-74; PMID:19197294; http://dx.doi.org/10.1038/nri2506
  • Baj-Krzyworzeka M, Baran J, Szatanek R, Stankiewicz D, Siedlar M, Zembala M. Prevention and reversal of tumor cell-induced monocyte deactivation by cytokines, purified protein derivative (PPD), and anti-IL-10 antibody. Cancer immun 2004; 4:8; PMID:15327279
  • Nishijima K-i, Hisatsune T, Minai Y, Kohyama M, Kaminogawa S. Anti-IL-10 Antibody Enhances the Proliferation of CD8+ T Cell Clones: Autoregulatory Role of Murine IL-10 in CD8+ T Cells. Cell Immunol 1994; 154:193-201; PMID:8118887; http://dx.doi.org/10.1006/cimm.1994.1068
  • Avradopoulos K, Mehta S, Blackinton D, Wanebo HJ. Interleukin-10 as a possible mediator of immunosuppressive effect in patients with squamous cell carcinoma of the head and neck. Ann Surg Oncol 1997; 4:184-90; PMID:9084857; http://dx.doi.org/10.1007/BF02303803
  • Sato T, Terai M, Tamura Y, Alexeev V, Mastrangelo MJ, Selvan SR. Interleukin 10 in the tumor microenvironment: a target for anticancer immunotherapy. Immunol Res 2011; 51:170-82; PMID:22139852; http://dx.doi.org/10.1007/s12026-011-8262-6
  • Lee TL, Yeh J, Van Waes C, Chen Z. Epigenetic modification of SOCS-1 differentially regulates STAT3 activation in response to interleukin-6 receptor and epidermal growth factor receptor signaling through JAK and/or MEK in head and neck squamous cell carcinomas. Mol Cancer Ther 2006; 5:8-19; PMID:16432158; http://dx.doi.org/10.1158/1535-7163.MCT-05-0069
  • Alexander WS. Suppressors of cytokine signalling (SOCS) in the immune system. Nat Rev Immunol 2002; 2:410-6; PMID:12093007
  • Yue P, Turkson J. Targeting STAT3 in cancer: how successful are we? 2009.
  • Wang S, Yang D, Lippman ME. Targeting Bcl-2 and Bcl-X L with nonpeptidic small-molecule antagonists. Semin Oncol, 2003; 30: 133-42; http://dx.doi.org/10.1053/j.seminoncol.2003.08.015
  • Mohammad RM, Wang S, Aboukameel A, Chen B, Wu X, Chen J, Al-Katib A. Preclinical studies of a nonpeptidic small-molecule inhibitor of Bcl-2 and Bcl-XL ; (−)-gossypol against diffuse large cell lymphoma. Mol Cancer Ther 2005; 4:13-21; PMID:15657349; http://dx.doi.org/10.1186/1476-4598-4-13
  • Mohammad RM, Goustin AS, Aboukameel A, Chen B, Banerjee S, Wang G, Nikolovska-Coleska Z, Wang S, Al-Katib A. Preclinical studies of TW-37, a new nonpeptidic small-molecule inhibitor of Bcl-2, in diffuse large cell lymphoma xenograft model reveal drug action on both Bcl-2 and Mcl-1. Clin Cancer Res 2007; 13:2226-35; PMID:17404107; http://dx.doi.org/10.1158/1078-0432.CCR-06-1574
  • Oh SA, Li MO. TGF-beta: guardian of T cell function. J Immunol 2013; 191:3973-9; PMID:24098055; http://dx.doi.org/10.4049/jimmunol.1301843
  • Gorelik L, Flavell RA. Immune-mediated eradication of tumors through the blockade of transforming growth factor-β signaling in T cells. Nat Med 2001; 7:1118-22; PMID:11590434; http://dx.doi.org/10.1038/nm1001-1118
  • Smyth MJ, Strobl S, Young H, Ortaldo J, Ochoa A. Regulation of lymphokine-activated killer activity and pore-forming protein gene expression in human peripheral blood CD8+ T lymphocytes. Inhibition by transforming growth factor-beta. J Immunol 1991; 146:3289-97; PMID:1827481
  • Cheng M-L, Chen H-W, Tsai J-P, Lee Y-P, Shih Y-C, Chang C-M, Ting CC. Clonal restriction of the expansion of antigen-specific CD8+ memory T cells by transforming growth factor-β. J leukocyte Biol 2006; 79:1033-42; PMID:16478921; http://dx.doi.org/10.1189/jlb.0805474
  • Letterio JJ, Roberts AB. Regulation of immune responses by TGF-β*. Ann Rev Immunol 1998; 16:137-61; PMID:9597127; http://dx.doi.org/10.1146/annurev.immunol.16.1.137
  • Bright JJ, Sriram S. TGF-β inhibits IL-12-induced activation of Jak-STAT pathway in T lymphocytes. J Immunol 1998; 161:1772-7; PMID:9712043
  • Holter W, Kalthoff F, Pickl W, Ebner C, Majdic O, Kraft D, Knapp W. Transforming growth factor-beta inhibits IL-4 and IFN-gamma production by stimulated human T cells. Int Immunol 1994; 6:469; PMID:8186198; http://dx.doi.org/10.1093/intimm/6.3.469
  • Peng Y, Laouar Y, Li MO, Green EA, Flavell RA. TGF-beta regulates in vivo expansion of Foxp3-expressing CD4+CD25+ regulatory T cells responsible for protection against diabetes. Proc Natl Acad Sci U S A 2004; 101:4572-7; PMID:15070759; http://dx.doi.org/10.1073/pnas.0400810101
  • Chen W, Jin W, Hardegen N, Lei K-j, Li L, Marinos N, McGrady G, Wahl SM. Conversion of peripheral CD4+ CD25− naive T cells to CD4+ CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3. J Exp Med 2003; 198:1875-86; PMID:14676299; http://dx.doi.org/10.1084/jem.20030152
  • Fantini MC, Becker C, Monteleone G, Pallone F, Galle PR, Neurath MF. Cutting edge: TGF-β induces a regulatory phenotype in CD4+ CD25− T cells through Foxp3 induction and down-regulation of Smad7. J Immunol 2004; 172:5149-53; PMID:15100250; http://dx.doi.org/10.4049/jimmunol.172.9.5149
  • Chalmin F, Mignot G, Bruchard M, Chevriaux A, Vegran F, Hichami A, Ladoire S, Derangère V, Vincent J, Masson D, et al. Stat3 and Gfi-1 transcription factors control Th17 cell immunosuppressive activity via the regulation of ectonucleotidase expression. Immunity 2012; 36:362-73; PMID:22406269; http://dx.doi.org/10.1016/j.immuni.2011.12.019
  • Kryczek I, Zhao E, Liu Y, Wang Y, Vatan L, Szeliga W, Moyer J, Klimczak A, Lange A, Zou W. Human TH17 cells are long-lived effector memory cells. Sci Trans Med 2011; 3:104ra0; http://dx.doi.org/10.1126/scitranslmed.3002949
  • Kryczek I, Banerjee M, Cheng P, Vatan L, Szeliga W, Wei S, Huang E, Finlayson E, Simeone D, Welling TH, et al. Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood 2009; 114:1141-9; PMID:19470694; http://dx.doi.org/10.1182/blood-2009-03-208249
  • Muranski P, Borman ZA, Kerkar SP, Klebanoff CA, Ji Y, Sanchez-Perez L, Sukumar M, Reger RN, Yu Z, Kern SJ, et al. Th17 cells are long lived and retain a stem cell-like molecular signature. Immunity 2011; 35:972-85; PMID:22177921; http://dx.doi.org/10.1016/j.immuni.2011.09.019
  • Martin-Orozco N, Muranski P, Chung Y, Yang XO, Yamazaki T, Lu S, Hwu P, Restifo NP, Overwijk WW, Dong C. T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity 2009; 31:787-98; PMID:19879162; http://dx.doi.org/10.1016/j.immuni.2009.09.014
  • Viaud S, Flament C, Zoubir M, Pautier P, LeCesne A, Ribrag V, Soria JC, Marty V, Vielh P, Robert C, et al. Cyclophosphamide induces differentiation of Th17 cells in cancer patients. Cancer Res 2011; 71:661-5; PMID:21148486; http://dx.doi.org/10.1158/0008-5472.CAN-10-1259
  • Hau P, Jachimczak P, Schlingensiepen R, Schulmeyer F, Jauch T, Steinbrecher A, Brawanski A, Proescholdt M, Schlaier J, Buchroithner J, et al. Inhibition of TGF-beta2 with AP 12009 in recurrent malignant gliomas: from preclinical to phase I/II studies. Oligonucleotides 2007; 17:201-12; PMID:17638524; http://dx.doi.org/10.1089/oli.2006.0053
  • Wojtowicz-Praga S. Reversal of tumor-induced immunosuppression by TGF-beta inhibitors. Invest New Drugs 2003; 21:21-32; PMID:12795527; http://dx.doi.org/10.1023/A:1022951824806
  • Connolly EC, Freimuth J, Akhurst RJ. Complexities of TGF-β targeted cancer therapy. Int J Biol Sci 2012; 8:964; PMID:22811618; http://dx.doi.org/10.7150/ijbs.4564
  • Sinha P, Clements VK, Fulton AM, Ostrand-Rosenberg S. Prostaglandin E2 promotes tumor progression by inducing myeloid-derived suppressor cells. Cancer Res 2007; 67:4507-13; PMID:17483367; http://dx.doi.org/10.1158/0008-5472.CAN-06-4174
  • Wang M-T, Honn KV, Nie D. Cyclooxygenases, prostanoids, and tumor progression. Cancer Meta Rev 2007; 26:525-34; PMID:17763971; http://dx.doi.org/10.1007/s10555-007-9096-5
  • Sreeramkumar V, Fresno M, Cuesta N. Prostaglandin E2 and T cells: friends or foes&quest. Immunol Cell Biol 2011; 90:579-86; PMID:21946663; http://dx.doi.org/10.1038/icb.2011.75
  • Betz M, Fox BS. Prostaglandin E2 inhibits production of Th1 lymphokines but not of Th2 lymphokines. J Immunol 1991; 146:108-13; PMID:1845802
  • Snijdewint F, Kaliński P, Wierenga E, Bos J, Kapsenberg M. Prostaglandin E2 differentially modulates cytokine secretion profiles of human T helper lymphocytes. J Immunol 1993; 150:5321-9; PMID:8390534
  • Huang M, Stolina M, Sharma S, Mao JT, Zhu L, Miller PW, Wollman J, Herschman H, Dubinett SM. Non-small cell lung cancer cyclooxygenase-2-dependent regulation of cytokine balance in lymphocytes and macrophages: up-regulation of interleukin 10 and down-regulation of interleukin 12 production. Cancer Res 1998; 58:1208-16; PMID:9515807
  • Stolina M, Sharma S, Lin Y, Dohadwala M, Gardner B, Luo J, Zhu L, Kronenberg M, Miller PW, Portanova J, et al. Specific inhibition of cyclooxygenase 2 restores antitumor reactivity by altering the balance of IL-10 and IL-12 synthesis. J Immunol 2000; 164:361-70; PMID:10605031; http://dx.doi.org/10.4049/jimmunol.164.1.361
  • Luo JS, Kammerer R, von Kleist S. Comparison of the effects of immunosuppressive factors from newly established colon carcinoma cell cultures on human lymphocyte proliferation and cytokine secretion. Tumour Biol 2000; 21:11-20; PMID:10601837; http://dx.doi.org/10.1159/000030106
  • Khan I, Al-Awadi F, Thomas N, Haridas S, Anim J. Cyclooxygenase-2 inhibition and experimental colitis: beneficial effects of phosphorothioated antisense oligonucleotide and meloxicam. Scand J Gastroenterol 2002; 37:1428-36; PMID:12523593; http://dx.doi.org/10.1080/003655202762671314
  • Tan W, Zhang W, Strasner A, Grivennikov S, Cheng JQ, Hoffman RM, Karin M. Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL-RANK signalling. Nature 2011; 470:548-53; PMID:21326202; http://dx.doi.org/10.1038/nature09707
  • Zhao E, Wang L, Dai J, Kryczek I, Wei S, Vatan L, Altuwaijri S, Sparwasser T, Wang G, Keller ET, et al. Regulatory T cells in the bone marrow microenvironment in patients with prostate cancer. Oncoimmunology 2012; 1:152-61; PMID:22720236; http://dx.doi.org/10.4161/onci.1.2.18480
  • Watanabe J, Kushihata F, Honda K, Sugita A, Tateishi N, Mominoki K, Matsuda S, Kobayashi N. Prognostic significance of Bcl-xL in human hepatocellular carcinoma. Surgery 2004; 135:604-12; PMID:15179366; http://dx.doi.org/10.1016/j.surg.2003.11.015
  • Altieri DC. Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene 2003; 22:8581-9; PMID:14634620; http://dx.doi.org/10.1038/sj.onc.1207113
  • Kleinberg L, Lie AK, Florenes VA, Nesland JM, Davidson B. Expression of inhibitor-of-apoptosis protein family members in malignant mesothelioma. Hum Pathol 2007; 38:986-94; PMID:17350081; http://dx.doi.org/10.1016/j.humpath.2006.12.013
  • Mizutani Y, Nakanishi H, Li YN, Matsubara H, Yamamoto K, Sato N, Shiraishi T, Nakamura T, Mikami K, Okihara K, et al. Overexpression of XIAP expression in renal cell carcinoma predicts a worse prognosis. Int J Oncol 2007; 30:919-25; PMID:17332931
  • Guan J, Chen J. Survivin-a new tumor-specific anti-apoptosis factor. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2001; 23:532-4; PMID:12905879
  • Pennati M, Folini M, Zaffaroni N. Targeting survivin in cancer therapy: fulfilled promises and open questions. Carcinogenesis 2007; 28:1133-9; PMID:17341657; http://dx.doi.org/10.1093/carcin/bgm047
  • Noh KH, Kang TH, Kim JH, Pai SI, Lin KY, Hung C-F, Wu TC, Kim TW. Activation of Akt as a mechanism for tumor immune evasion. Mol Ther 2008; 17:439-47; PMID:19107122; http://dx.doi.org/10.1038/mt.2008.255
  • Yu H, Kortylewski M, Pardoll D. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol 2007; 7:41-51; PMID:17186030; http://dx.doi.org/10.1038/nri1995
  • Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL, Chen S, Klein AP, Pardoll DM, Topalian SL, et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Trans Med 2012; 4:127ra37; PMID:22461641; http://dx.doi.org/10.1126/scitranslmed.3003689
  • Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366:2443-54; PMID:22658127; http://dx.doi.org/10.1056/NEJMoa1200690
  • Topalian SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol 2012; 24:207-12; PMID:22236695; http://dx.doi.org/10.1016/j.coi.2011.12.009
  • Cao Y, Zhang L, Ritprajak P, Tsushima F, Youngnak-Piboonratanakit P, Kamimura Y, Hashiguchi M, Azuma M. Immunoregulatory molecule B7-H1 (CD274) contributes to skin carcinogenesis. Cancer Res 2011; 71:4737-41; PMID:21730022; http://dx.doi.org/10.1158/0008-5472.CAN-11-0527
  • Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 2008; 26:677-704; PMID:18173375; http://dx.doi.org/10.1146/annurev.immunol.26.021607.090331
  • Francisco LM, Sage PT, Sharpe AH. The PD-1 pathway in tolerance and autoimmunity. Immunol Rev 2010; 236:219-42; PMID:20636820; http://dx.doi.org/10.1111/j.1600-065X.2010.00923.x
  • Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 2002; 8:793-800; PMID:12091876; http://dx.doi.org/10.1038/nm0902-1039c
  • Sugasawa H, Ichikura T, Tsujimoto H, Kinoshita M, Morita D, Ono S, Chochi K, Tsuda H, Seki S, Mochizuki H. Prognostic significance of expression of CCL5/RANTES receptors in patients with gastric cancer. J Surg Oncol 2008; 97:445-50; PMID:18297689; http://dx.doi.org/10.1002/jso.20984
  • Curiel TJ, Wei S, Dong H, Alvarez X, Cheng P, Mottram P, Krzysiek R, Knutson KL, Daniel B, Zimmermann MC, et al. Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 2003; 9:562-7; PMID:12704383; http://dx.doi.org/10.1038/nm863
  • Kryczek I, Zou L, Rodriguez P, Zhu G, Wei S, Mottram P, Brumlik M, Cheng P, Curiel T, Myers L, et al. B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J Exp Med 2006; 203:871-81; PMID:16606666; http://dx.doi.org/10.1084/jem.20050930
  • Strome SE, Dong H, Tamura H, Voss SG, Flies DB, Tamada K, Salomao D, Cheville J, Hirano F, Lin W, et al. B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma. Cancer Res 2003; 63:6501-5; PMID:14559843
  • Li N, Qin H, Li X, Zhou C, Wang D, Ma W, Lin C, Zhang Y, Wang S, Zhang S. Potent systemic antitumor immunity induced by vaccination with chemotactic-prostate tumor associated antigen gene-modified tumor cell and blockade of B7-H1. J Clin Immunol 2007; 27:117-30; PMID:17180470; http://dx.doi.org/10.1007/s10875-006-9053-z
  • Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 2013; 369:134-44; PMID:23724846; http://dx.doi.org/10.1056/NEJMoa1305133
  • Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, Stankevich E, Pons A, Salay TM, McMiller TL, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 2010; 28:3167-75; PMID:20516446; http://dx.doi.org/10.1200/JCO.2009.26.7609
  • Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012; 366:2455-65; PMID:22658128; http://dx.doi.org/10.1056/NEJMoa1200694
  • Flies DB, Sandler BJ, Sznol M, Chen L. Blockade of the B7-H1/PD-1 pathway for cancer immunotherapy. The Yale J Biol Med 2011; 84:409; PMID:22180678
  • Ascierto PA, Simeone E, Sznol M, Fu Y-X, Melero I. Clinical experiences with anti-CD137 and anti-PD1 therapeutic antibodies. Semin Oncol 2010; 37:508-16; http://dx.doi.org/10.1053/j.seminoncol.2010.09.008
  • Ichikawa M, Chen L. Role of B7-H1 and B7-H4 molecules in down-regulating effector phase of T-cell immunity: novel cancer escaping mechanisms. Front Biosci 2005; 10:2856-60; PMID:15970540; http://dx.doi.org/10.2741/1742
  • Geng H, Zhang GM, Xiao H, Yuan Y, Li D, Zhang H, Qiu H, He YF, Feng ZH. HSP70 vaccine in combination with gene therapy with plasmid DNA encoding sPD-1 overcomes immune resistance and suppresses the progression of pulmonary metastatic melanoma. Int J Cancer 2006; 118:2657-64; PMID:16425224; http://dx.doi.org/10.1002/ijc.21795
  • Soares KC, Zheng L, Edil B, Jaffee EM. Vaccines for pancreatic cancer. Cancer J (Sudbury, Mass) 2012; 18:642; PMID:23187853; http://dx.doi.org/10.1097/PPO.0b013e3182756903
  • Smith JB, Stashwick C, Powell DJ, Jr. B7-H4 as a potential target for immunotherapy for gynecologic cancers: a closer look. Gynecol Oncol 2014; 134:181-9; PMID:24657487; http://dx.doi.org/10.1016/j.ygyno.2014.03.553
  • Sica GL, Choi IH, Zhu G, Tamada K, Wang SD, Tamura H, Chapoval AI, Flies DB, Bajorath J, Chen L. B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity 2003; 18:849-61; PMID:12818165; http://dx.doi.org/10.1016/S1074-7613(03)00152-3
  • Murooka TT, Wong MM, Rahbar R, Majchrzak-Kita B, Proudfoot AE, Fish EN. CCL5-CCR5-mediated Apoptosis in T cells requirement for glycosaminoglycan binding and CCL5 aggregation. J Biol Chem 2006; 281:25184-94; PMID:16807236; http://dx.doi.org/10.1074/jbc.M603912200
  • Roth W, Reed JC. FLIP protein and TRAIL-induced apoptosis. Vitamins & Hormones 2004; 67:189-206; PMID:15110178; http://dx.doi.org/10.1016/S0083-6729(04)67011-7
  • French LE, Tschopp J. The TRAIL to selective tumor death. Nat Med 1999; 5:146-7; PMID:9930856; http://dx.doi.org/10.1038/5505
  • Wang S, El-Deiry WS. TRAIL and apoptosis induction by TNF-family death receptors. Oncogene 2003; 22:8628-33; PMID:14634624; http://dx.doi.org/10.1038/sj.onc.1207232
  • Marsters SA, Pitti RM, Donahue CJ, Ruppert S, Bauer KD, Ashkenazi A. Activation of apoptosis by Apo-2 ligand is independent of FADD but blocked by CrmA. Curr Biol 1996; 6:750-2; PMID:8793301; http://dx.doi.org/10.1016/S0960-9822(09)00456-4
  • Jeremias I, Herr I, Boehler T, Debatin KM. TRAIL/Apo‐2‐ligand‐induced apoptosis in human T cells. Euro J Immunol 1998; 28:143-52; PMID:9485194; http://dx.doi.org/10.1002/(SICI)1521-4141(199801)28:01%3c143::AID-IMMU143%3e3.0.CO;2-3
  • Hallermalm K, De Geer A, Kiessling R, Levitsky V, Levitskaya J. Autocrine secretion of Fas ligand shields tumor cells from Fas-mediated killing by cytotoxic lymphocytes. Cancer Res 2004; 64:6775-82; PMID:15374996; http://dx.doi.org/10.1158/0008-5472.CAN-04-0508
  • Schall TJ, Bacon KB. Chemokines, leukocyte trafficking, and inflammation. Curr Opin Immunol 1994; 6:865-73; PMID:7710711; http://dx.doi.org/10.1016/0952-7915(94)90006-X
  • Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies-integrating mammalian biology. Cell 2001; 104:487-501; PMID:11239407; http://dx.doi.org/10.1016/S0092-8674(01)00237-9
  • Rubinstein N, Alvarez M, Zwirner NW, Toscano MA, Ilarregui JM, Bravo A, Mordoh J, Fainboim L, Podhajcer OL, Rabinovich GA. Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection; A potential mechanism of tumor-immune privilege. Cancer Cell 2004; 5:241-51; PMID:15050916; http://dx.doi.org/10.1016/S1535-6108(04)00024-8
  • Giovarelli M, Musiani P, Garotta G, Ebner R, Di Carlo E, Kim Y, Cappello P, Rigamonti L, Bernabei P, Novelli F, et al. A “stealth effect”: adenocarcinoma cells engineered to express TRAIL elude tumor-specific and allogeneic T cell reactions. J Immunol 1999; 163:4886-93; PMID:10528190
  • Nakashima M, Sonoda K, Watanabe T. Inhibition of cell growth and induction of apoptotic cell death by the human tumor-associated antigen RCAS1. Nat Med 1999; 5:938-42; PMID:10426319; http://dx.doi.org/10.1038/11383
  • Umata T, Hirata M, Takahashi T, Ryu F, Shida S, Takahashi Y, Tsuneoka M, Miura Y, Masuda M, Horiguchi Y, et al. A dual signaling cascade that regulates the ectodomain shedding of heparin-binding epidermal growth factor-like growth factor. J Biol Chem 2001; 276:30475-82; PMID:11402047; http://dx.doi.org/10.1074/jbc.M103673200
  • Igney FH, Behrens CK, Krammer PH. CD95L mediates tumor counterattack in vitro but induces neutrophil-independent tumor rejection in vivo. Int J Cancer 2005; 113:78-87; PMID:15386427; http://dx.doi.org/10.1002/ijc.20538
  • Ryan AE, Shanahan F, O'Connell J, Houston AM. Addressing the “Fas counterattack” controversy: blocking fas ligand expression suppresses tumor immune evasion of colon cancer in vivo. Cancer Res 2005; 65:9817-23; PMID:16267003; http://dx.doi.org/10.1158/0008-5472.CAN-05-1462
  • Aubrey M. Glycans in cell interaction and recognition. CRC Press, 2003.
  • Elola M, Wolfenstein-Todel C, Troncoso M, Vasta G, Rabinovich G. Galectins: matricellular glycan-binding proteins linking cell adhesion, migration, and survival. Cell Mol Life Sci 2007; 64:1679-700; PMID:17497244; http://dx.doi.org/10.1007/s00018-007-7044-8
  • Moiseeva EP, Spring EL, Baron JH, de Bono D. Galectin 1 modulates attachment, spreading and migration of cultured vascular smooth muscle cells via interactions with cellular receptors and components ofextracellu lar matrix. J Vasc Res 1999; 36:47-58; PMID:10050073; http://dx.doi.org/10.1159/000025625
  • Liu F-T. Galectins: a new family of regulators of inflammation. Clin Immunol 2000; 97:79-88; PMID:11027447; http://dx.doi.org/10.1006/clim.2000.4912
  • Liu F-T. Regulatory roles of galectins in the immune response. Int Arch Allergy Immunol 2005; 136:385-400; PMID:15775687; http://dx.doi.org/10.1159/000084545
  • Thijssen VL, Postel R, Brandwijk RJ, Dings RP, Nesmelova I, Satijn S, Verhofstad N, Nakabeppu Y, Baum LG, Bakkers J, et al. Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy. Proc Natl Acad Sci 2006; 103:15975-80; http://dx.doi.org/10.1073/pnas.0603883103
  • Thijssen VL, Barkan B, Shoji H, Aries IM, Mathieu V, Deltour L, Hackeng TM, Kiss R, Kloog Y, Poirier F, et al. Tumor cells secrete galectin-1 to enhance endothelial cell activity. Cancer Res 2010; 70:6216-24; PMID:20647324; http://dx.doi.org/10.1158/0008-5472.CAN-09-4150
  • Paz A, Haklai R, Elad-Sfadia G, Ballan E, Kloog Y. Galectin-1 binds oncogenic H-Ras to mediate Ras membrane anchorage and cell transformation. Oncogene 2001; 20:7486-93; PMID:11709720; http://dx.doi.org/10.1038/sj.onc.1204950
  • van den Brule FA, Waltregny D, Castronovo V. Increased expression of galectin-1 in carcinoma-associated stroma predicts poor outcome in prostate carcinoma patients. J Pathol 2001; 193:80-7; PMID:11169519; http://dx.doi.org/10.1002/1096-9896(2000)9999:9999%3c::AID-PATH730%3e3.0.CO;2-2
  • Langbein S, Brade J, Badawi JK, Hatzinger M, Kaltner H, Lensch M, Specht K, André S, Brinck U, Alken P, et al. Gene-expression signature of adhesion/growth-regulatory tissue lectins (galectins) in transitional cell cancer and its prognostic relevance. Histopathology 2007; 51:681-90; PMID:17927590; http://dx.doi.org/10.1111/j.1365-2559.2007.02852.x
  • Chen J, Zhou S-J, Zhang Y, Zhang G-Q, Zha T-Z, Feng Y-Z, Zhang K. Clinicopathological and prognostic significance of galectin-1 and vascular endothelial growth factor expression in gastric cancer. World J Gastroenterol 2013; 19:2073; PMID:23599627; http://dx.doi.org/10.3748/wjg.v19.i13.2073
  • Astorgues-Xerri L, Riveiro ME, Tijeras-Raballand A, Serova M, Neuzillet C, Albert S, Raymond E, Faivre S. Unraveling galectin-1 as a novel therapeutic target for cancer. Cancer Treat Rev 2014; 40:307-19; PMID:23953240; http://dx.doi.org/10.1016/j.ctrv.2013.07.007
  • Danguy A, Camby I, Kiss R. Galectins and cancer. Biochimica et Biophysica Acta (BBA)-General Subjects 2002; 1572:285-93; http://dx.doi.org/10.1016/S0304-4165(02)00315-X
  • Vespa GN, Lewis LA, Kozak KR, Moran M, Nguyen JT, Baum LG, Miceli MC. Galectin-1 specifically modulates TCR signals to enhance TCR apoptosis but inhibit IL-2 production and proliferation. J Immunol 1999; 162:799-806; PMID:9916701
  • Blaskó A, Fajka-Boja R, Ion G, Monostori É. How does it act when soluble? Critical evaluation of mechanism of galectin-1 induced T-cell apoptosis. Acta Biologica Hungarica 2011; 62:106-11; http://dx.doi.org/10.1556/ABiol.61.2011.1.11
  • Pang M, He J, Johnson P, Baum LG. CD45-mediated fodrin cleavage during galectin-1 T cell death promotes phagocytic clearance of dying cells. J Immunol 2009; 182:7001-8; PMID:19454697; http://dx.doi.org/10.4049/jimmunol.0804329
  • Perillo NL, Pace KE, Seilhamer JJ, Baum LG. Apoptosis of T cells mediated by galectin-1. Nature 1995; 378:736-9.
  • Walzel H, Schulz U, Neels P, Brock J. Galectin-1, a natural ligand for the receptor-type protein tyrosine phosphatase CD45. Immunol Lett 1999; 67:193-202; PMID:10369126; http://dx.doi.org/10.1016/S0165-2478(99)00012-7
  • Fajka-Boja R, Szemes M, Ion G, Légrádi Á, Caron M, Monostori É. Receptor tyrosine phosphatase, CD45 binds galectin-1 but does not mediate its apoptotic signal in T cell lines. Immunol Lett 2002; 82:149-54; PMID:12008046; http://dx.doi.org/10.1016/S0165-2478(02)00030-5
  • Nguyen JT, Evans DP, Galvan M, Pace KE, Leitenberg D, Bui TN, Baum LG. CD45 modulates galectin-1-induced T cell death: regulation by expression of core 2 O-glycans. J Immunol 2001; 167:5697-707; PMID:11698442; http://dx.doi.org/10.4049/jimmunol.167.10.5697
  • Pace KE, Hahn HP, Pang M, Nguyen JT, Baum LG. Cutting edge: CD7 delivers a pro-apoptotic signal during galectin-1-induced T cell death. J Immunol 2000; 165:2331-4; PMID:10946254; http://dx.doi.org/10.4049/jimmunol.165.5.2331
  • Le Q-T, Shi G, Cao H, Nelson DW, Wang Y, Chen EY, Zhao S, Kong C, Richardson D, O'Byrne KJ, et al. Galectin-1: a link between tumor hypoxia and tumor immune privilege. J Clin Oncol 2005; 23:8932-41; PMID:16219933; http://dx.doi.org/10.1200/JCO.2005.02.0206
  • Banh A, Zhang J, Cao H, Bouley DM, Kwok S, Kong C, Giaccia AJ, Koong AC, Le QT. Tumor galectin-1 mediates tumor growth and metastasis through regulation of T-cell apoptosis. Cancer Res 2011; 71:4423-31; PMID:21546572; http://dx.doi.org/10.1158/0008-5472.CAN-10-4157
  • He J, Baum LG. Presentation of galectin-1 by extracellular matrix triggers T cell death. J Biol Chem 2004; 279:4705-12; PMID:14617626; http://dx.doi.org/10.1074/jbc.M311183200
  • Kovacs-Solyom F, Blasko A, Fajka-Boja R, Katona RL, Vegh L, Novak J, Szebeni GJ, Krenács L, Uher F, Tubak V, et al. Mechanism of tumor cell-induced T-cell apoptosis mediated by galectin-1. Immunol Lett 2010; 127:108-18; PMID:19874850; http://dx.doi.org/10.1016/j.imlet.2009.10.003
  • Le Mercier M, Mathieu V, Haibe-Kains B, Bontempi G, Mijatovic T, Decaestecker C, Kiss R, Lefranc F. Knocking down galectin 1 in human hs683 glioblastoma cells impairs both angiogenesis and endoplasmic reticulum stress responses. J Neuropathol Exp Neurol 2008; 67:456-69; PMID:18431251; http://dx.doi.org/10.1097/NEN.0b013e318170f892
  • Jung T-Y, Jung S, Ryu H-H, Jeong Y-I, Jin Y-H, Jin S-G, Kim IY, Kang SS, Kim HS. Role of galectin-1 in migration and invasion of human glioblastoma multiforme cell lines. J Neurosurg 2008; 109:273-84.
  • Saussez S, Decaestecker C, Lorfevre F, Cucu D-R, Mortuaire G, Chevalier D, Wacreniez A, Kaltner H, André S, Toubeau G, et al. High level of galectin-1 expression is a negative prognostic predictor of recurrence in laryngeal squamous cell carcinomas. Int J Oncol 2007; 30:1109-18; PMID:17390012
  • Saussez S, Camby I, Toubeau G, Kiss R. Galectins as modulators of tumor progression in head and neck squamous cell carcinomas. Head Neck 2007; 29:874-84; PMID:17315170; http://dx.doi.org/10.1002/hed.20559
  • He J, Baum LG. Endothelial cell expression of galectin-1 induced by prostate cancer cells inhibits T-cell transendothelial migration. Lab Invest 2006; 86:578-90; PMID:16607379
  • Thijssen VL, Hulsmans S, Griffioen AW. The galectin profile of the endothelium: altered expression and localization in activated and tumor endothelial cells. Am J Pathol 2008; 172:545-53; PMID:18202194; http://dx.doi.org/10.2353/ajpath.2008.070938
  • Matarrese P, Tinari A, Mormone E, Bianco GA, Toscano MA, Ascione B, Rabinovich GA, Malorni W. Galectin-1 sensitizes resting human T lymphocytes to Fas (CD95)-mediated cell death via mitochondrial hyperpolarization, budding, and fission. J Biol Chem 2005; 280:6969-85; PMID:15556941; http://dx.doi.org/10.1074/jbc.M409752200
  • Cedeno-Laurent F, Opperman M, Barthel SR, Kuchroo VK, Dimitroff CJ. Galectin-1 triggers an immunoregulatory signature in Th cells functionally defined by IL-10 expression. J Immunol 2012; 188:3127-37; PMID:22345665; http://dx.doi.org/10.4049/jimmunol.1103433
  • Croci DO, Salatino M, Rubinstein N, Cerliani JP, Cavallin LE, Leung HJ, Ouyang J, Ilarregui JM, Toscano MA, Domaica CI, et al. Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis and tumorigenesis in Kaposi's sarcoma. J Exp Med 2012; 209:1985-2000; PMID:23027923; http://dx.doi.org/10.1084/jem.20111665
  • Heslop HE. A less sour sweet; blocking galectin. Blood 2011; 117:4165-6; PMID:21511962; http://dx.doi.org/10.1182/blood-2011-03-337683
  • Ito K, Scott SA, Cutler S, Dong L-F, Neuzil J, Blanchard H, Ralph SJ. Thiodigalactoside inhibits murine cancers by concurrently blocking effects of galectin-1 on immune dysregulation, angiogenesis and protection against oxidative stress. Angiogenesis 2011; 14:293-307; PMID:21523436; http://dx.doi.org/10.1007/s10456-011-9213-5
  • Delaine T, Cumpstey I, Ingrassia L, Mercier ML, Okechukwu P, Leffler H, Kiss R, Nilsson UJ. Galectin-inhibitory thiodigalactoside ester derivatives have antimigratory effects in cultured lung and prostate cancer cells. J Med Chem 2008; 51:8109-14; PMID:19053747; http://dx.doi.org/10.1021/jm801077j
  • Iurisci I, Cumashi A, Sherman AA, Tsvetkov YE, Tinari N, Piccolo E, D'Egidio M, Adamo V, Natoli C, Rabinovich GA, et al. Synthetic inhibitors of galectin-1 and-3 selectively modulate homotypic cell aggregation and tumor cell apoptosis. Anticancer Res 2009; 29:403-10; PMID:19331179
  • Rabinovich GA, Cumashi A, Bianco GA, Ciavardelli D, Iurisci I, D'Egidio M, Piccolo E, Tinari N, Nifantiev N, Iacobelli S. Synthetic lactulose amines: novel class of anticancer agents that induce tumor-cell apoptosis and inhibit galectin-mediated homotypic cell aggregation and endothelial cell morphogenesis. Glycobiology 2006; 16:210-20; PMID:16282605; http://dx.doi.org/10.1093/glycob/cwj056
  • Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 1997; 91:479-89; PMID:9390557; http://dx.doi.org/10.1016/S0092-8674(00)80434-1
  • Mellado M, de Ana AMn, Moreno MC, Martínez-A C, Rodríguez-Frade JM. A potential immune escape mechanism by melanoma cells through the activation of chemokine-induced T cell death. Curr Biol 2001; 11:691-6; PMID:11369232; http://dx.doi.org/10.1016/S0960-9822(01)00199-3
  • Lin S, Wan S, Sun L, Hu J, Fang D, Zhao R, Yuan S, Zhang L. Chemokine C‐C motif receptor 5 and C‐C motif ligand 5 promote cancer cell migration under hypoxia. Cancer Sci 2012; 103:904-12; PMID:22380870; http://dx.doi.org/10.1111/j.1349-7006.2012.02259.x
  • Mrowietz U, Schwenk U, Maune S, Bartels J, Küpper M, Fichtner I, Schröder JM, Schadendorf D. The chemokine RANTES is secreted by human melanoma cells and is associated with enhanced tumour formation in nude mice. British J Cancer 1999; 79:1025; PMID:10098731; http://dx.doi.org/10.1038/sj.bjc.6690164
  • Aldinucci D, Colombatti A. The inflammatory chemokine CCL5 and cancer progression. Mediators Inflamm 2014; 2014; PMID:24523569; http://dx.doi.org/10.1155/2014/292376
  • Kato T, Fujita Y, Nakane K, Mizutani K, Terazawa R, Ehara H, Kanimoto Y, Kojima T, Nozawa Y, Deguchi T, et al. CCR1/CCL5 interaction promotes invasion of taxane-resistant PC3 prostate cancer cells by increasing secretion of MMPs 2/9 and by activating ERK and Rac signaling. Cytokine 2013; 64:251-7; PMID:23876400; http://dx.doi.org/10.1016/j.cyto.2013.06.313
  • Yaal-Hahoshen N, Shina S, Leider-Trejo L, Barnea I, Shabtai EL, Azenshtein E, Greenberg I, Keydar I, Ben-Baruch A. The chemokine CCL5 as a potential prognostic factor predicting disease progression in stage II breast cancer patients. Clin Cancer Res 2006; 12:4474-80; PMID:16899591; http://dx.doi.org/10.1158/1078-0432.CCR-06-0074
  • Lv D, Zhang Y, Kim H-J, Zhang L, Ma X. CCL5 as a potential immunotherapeutic target in triple-negative breast cancer. Cell Mol Immunol 2013; 10:303-10; PMID:23376885; http://dx.doi.org/10.1038/cmi.2012.69
  • Sugasawa H, Ichikura T, Kinoshita M, Ono S, Majima T, Tsujimoto H, Chochi K, Hiroi S, Takayama E, Saitoh D, et al. Gastric cancer cells exploit CD4+ cell‐derived CCL5 for their growth and prevention of CD8+ cell‐involved tumor elimination. Int J Cancer 2008; 122:2535-41; http://dx.doi.org/10.1002/ijc.23401
  • Chang L-Y, Lin Y-C, Mahalingam J, Huang C-T, Chen T-W, Kang C-W, Peng HM, Chu YY, Chiang JM, Dutta A, et al. Tumor-Derived Chemokine CCL5 Enhances TGF-β-Mediated Killing of CD8+ T Cells in Colon Cancer by T-Regulatory Cells. Cancer Res 2012; 72:1092-102; PMID:22282655; http://dx.doi.org/10.1158/0008-5472.CAN-11-2493
  • Zhang Y, Zhu J, Hong X, Zhou Y, Ren K, Shu X, Wang Q. The membrane molecule RCAS1 induces immune cell apoptosis via the RCAS1-RCAS1R pathway. Int J Mol Med 2013; 31:1319-26; PMID:23563217
  • Matsushima T, Nakashima M, Oshima K, Abe Y, Nishimura J, Nawata H, Watanabe T, Muta K. Receptor binding cancer antigen expressed on SiSo cells, a novel regulator of apoptosis of erythroid progenitor cells. Blood 2001; 98:313-21; PMID:11435298; http://dx.doi.org/10.1182/blood.V98.2.313
  • Okada K, Nakashima M, Komuta K, Hashimoto S, Okudaira S, Baba N, Hishikawa Y, Koji T, Kanematsu T, Watanabe T. Expression of tumor-associated membrane antigen, RCAS1, in human colorectal carcinomas and possible role in apoptosis of tumor-infiltrating lymphocytes. Modern Pathol 2003; 16:679-85; PMID:12861064; http://dx.doi.org/10.1097/01.MP.0000074732.17945.6C
  • Han Y, Qin W, Huang G. Knockdown of RCAS1 expression by RNA interference recovers T cell growth and proliferation. Cancer Lett 2007; 257:182-90; PMID:17825484; http://dx.doi.org/10.1016/j.canlet.2007.07.016

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