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Immunological Investigations
A Journal of Molecular and Cellular Immunology
Volume 41, 2012 - Issue 6-7
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Research Article

Myeloid-Derived Suppressor Cells and anti-tumor T cells: a complex relationship

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Pages 595-613 | Published online: 27 Sep 2012

REFERENCES

  • Almand, B., Clark, J. I., Nikitina, E., van Beynen, J., English, N.R., Knight, S. C., Carbone, D.P., Gabrilovich, D. I. (2001). Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J. Immunol. 166:678–689.
  • Arner, E. S., Holmgren, A. (2000). Physiological functions of thioredoxin and thioredoxin reductase. Eur. J. Biochem. 267:6102–6109.
  • Bannai, S. (1984). Transport of cystine and cysteine in mammalian cells. Biochim Biophys Acta 779:289–306.
  • Bogdan, C. (2001). Nitric oxide and the immune response. Nat. Immunol. 2:907–916.
  • Brito, C., Naviliat, M., Tiscornia, A. C., Vuillier, F., Gualco, G., Dighiero, G., Radi, R., Cayota, A. M. (1999). Peroxynitrite inhibits T lymphocyte activation and proliferation by promoting impairment of tyrosine phosphorylation and peroxynitrite-driven apoptotic death. J. Immunol. 162:3356–3366.
  • Bronte, V. (2009). Myeloid-derived suppressor cells in inflammation: uncovering cell subsets with enhanced immunosuppressive functions. Eur. J. Immunol. 39:2670–2672.
  • Bronte, V., Chappell, D. B., Apolloni, E., Cabrelle, A., Wang, M., Hwu, P., Restifo, N. P. (1999). Unopposed production of granulocyte-macrophage colony-stimulating factor by tumors inhibits CD8+ T cell responses by dysregulating antigen-presenting cell maturation. J. Immunol. 162:5728–5737.
  • Bronte, V., Serafini, P., Mazzoni, A., Segal, D.M., Zanovello, P. (2003). L-arginine metabolism in myeloid cells controls T-lymphocyte functions. Trends Immunol. 24:302–306.
  • Brys, L., Beschin, A., Raes, G., Ghassabeh, G.H., Noel, W., Brandt, J., Brombacher, F., De Baetselier, P. (2005). Reactive oxygen species and 12/15-lipoxygenase contribute to the antiproliferative capacity of alternatively activated myeloid cells elicited during helminth infection. J. Immunol. 174:6095–6104.
  • Cederbaum, S. D., Yu, H., Grody, W. W., Kern, R. M., Yoo, P. Iyer, R. K. (2004). Arginases I and II: do their functions overlap? Mol Genet Metab 81 Suppl 1:S38–44.
  • Chang, C. I., J. C. Liao, and L. Kuo. (2001). Macrophage arginase promotes tumor cell growth and suppresses nitric oxide-mediated tumor cytotoxicity. Cancer Res 61:1100–1106.
  • Cheng, P., Corzo, C.A., Luetteke, N., Yu, B., Nagaraj, S., Bui, M. M. Ortiz, M., Nacken, W., Sorg, C., Vogl, T., Roth, J., Gabrilovich, D. I. (2008). Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein. J. Exp. Med. 205:2235–2249.
  • Coley, W. (1894). Treatment of inoperable malignant tumors with the toxines of erysipelas and the bacillus prodigiosus. Trans. Am. Surg. Assoc. 12:183–212.
  • Corzo, C. A., Condamine, T., Lu, L., Cotter, M. J., Youn, J. I., Cheng, P., Cho, H. I., Celis, E., Quiceno, D.G., T. Padhya, T. V. McCaffrey, J. C. McCaffrey, D. I. Gabrilovich. (2010). HIF-1alpha regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J. Exp. Med. 207:2439–2453.
  • De Santo, C., P. Serafini, I. Marigo, L. Dolcetti, M. Bolla, P. Del Soldato, C. Melani, C. Guiducci, M. P. Colombo, M. Iezzi, P. Musiani, P. Zanovello, V. Bronte. (2005). Nitroaspirin corrects immune dysfunction in tumor-bearing hosts and promotes tumor eradication by cancer vaccination. Proc. Natl. Acad. Sci. U S A 102:4185–4190.
  • Eagle, H., C. Washington, S. M. Friedman. (1966). The synthesis of homocystine, cystathionine, and cystine by cultured diploid and heteroploid human cells. Proc. Natl. Acad. Sci. U S A 56:156–163.
  • Ferris, R. L., E. M. Jaffee, S. Ferrone. (2010). Tumor antigen-targeted, monoclonal antibody-based immunotherapy: clinical response, cellular immunity, and immunoescape. J. Clin. Oncol. 28:4390–4399.
  • Franco, J. L., P. Ghosh, R. H. Wiltrout, C. R. Carter, A. H. Zea, N. Momozaki, A. C. Ochoa, D. L. Longo, T. J. Sayers, K. L. KoMDSChlies. (1995). Partial degradation of T-cell signal transduction molecules by contaminating granulocytes during protein extraction of splenic T cells from tumor-bearing mice. Cancer Res. 55:3840–3846.
  • Frey, A. B., Monu, N. (2006). Effector-phase tolerance: another mechanism of how cancer escapes antitumor immune response. J. Leukoc. Biol. 79:652–662.
  • Gabrilovich, D. (2004). Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nat. Rev. Immunol. 4:941–952.
  • Gabrilovich, D., Hurwitz, A. (2008). Immune suppression in cancer. Springer Press, New York.
  • Gabrilovich, D., T. Ishida, T. Oyama, S. Ran, V. Kravtsov, S. Nadaf, D. P. Carbone. (1998). Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 92:4150–4166.
  • Gabrilovich, D. I., H. L. Chen, K. R. Girgis, H. T. Cunningham, G. M. Meny, S. Nadaf, D. Kavanaugh, D. P. Carbone. (1996). Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat. Med. 2:1096–1103.
  • Gabrilovich, D. I., J. Corak, I. F. Ciernik, D. Kavanaugh, D. P. Carbone. (1997). Decreased antigen presentation by dendritic cells in patients with breast cancer. Clin. Cancer Res. 3:483–490.
  • Gabrilovich, D. I., Nagaraj, S. (2009). Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol. 9:162–174.
  • Gabrilovich, D. I., M. P. Velders, E. M. Sotomayor, and W. M. Kast. (2001). Mechanism of immune dysfunction in cancer mediated by immature Gr-1+ myeloid cells. J Immunol 166:5398–5406.
  • Gallina, G., L. Dolcetti, P. Serafini, C. De Santo, I. Marigo, M. P. Colombo, G. Basso, F. Brombacher, I. Borrello, P. Zanovello, S. Bicciato, and V. Bronte. (2006). Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells. J. Clin. Invest. 116:2777–2790.
  • Geldmacher, A., A. Freier, F. O. Losch, Walden, P. (2011). Therapeutic vaccination for cancer immunotherapy: antigen selection and clinical responses. Hum. Vaccin. 7 Suppl:115–119.
  • Gmunder, H., H. P. Eck, B. Benninghoff, S. Roth, Droge, W. (1990). Macrophages regulate intracellular glutathione levels of lymphocytes. Evidence for an immunoregulatory role of cysteine. Cell Immunol. 129:32–46.
  • Gmunder, H., H. P. Eck, Droge, W. (1991). Low membrane transport activity for cystine in resting and mitogenically stimulated human lymphocyte preparations and human T cell clones. Eur. J. Biochem. 201:113–117.
  • Gout, P. W., A. R. Buckley, C. R. Simms, Bruchovsky, N. (2001). Sulfasalazine, a potent suppressor of lymphoma growth by inhibition of the x(c)- cystine transporter: a new action for an old drug. Leukemia 15:1633–1640.
  • Grohmann, U., F. Fallarino, Puccetti, P. (2003). Tolerance, DCs and tryptophan: much ado about IDO. Trends Immunol. 24:242–248.
  • Gurtner, G. J., R. D. Newberry, S. R. Schloemann, K. G. McDonald, Stenson, W. F. (2003). Inhibition of indoleamine 2,3-dioxygenase augments trinitrobenzene sulfonic acid colitis in mice. Gastroenterology 125:1762–1773.
  • Hanson, E. M., V. K. Clements, P. Sinha, D. Ilkovitch, and S. Ostrand-Rosenberg. (2009). Myeloid-derived suppressor cells down-regulate L-selectin expression on CD4+ and CD8+ T cells. J. Immunol. 183:937–944.
  • Hayashi, T., L. Beck, C. Rossetto, X. Gong, O. Takikawa, K. Takabayashi, D. H. Broide, D. A. Carson, Raz, E. (2004). Inhibition of experimental asthma by indoleamine 2,3-dioxygenase. J. Clin. Invest. 114:270–279.
  • Huang, B., P. Y. Pan, Q. Li, A. I. Sato, D. E. Levy, J. Bromberg, C. M. Divino, Chen, S. H.. (2006). Gr-1+CD115+ immature Myeloid-Derived Suppressor Cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res 66:1123–1131.
  • Hwu, P., M. X. Du, R. Lapointe, M. Do, M. W. Taylor, Young, H. A. (2000). Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation. J. Immunol. 164:3596–3599.
  • Ishii, I., N. Akahoshi, X. N. Yu, Y. Kobayashi, K. Namekata, G. Komaki, Kimura, H. (2004). Murine cystathionine gamma-lyase: complete cDNA and genomic sequences, promoter activity, tissue distribution and developmental expression. Biochem. J. 381:113–123.
  • Iwata, S., T. Hori, N. Sato, Y. Ueda-Taniguchi, T. Yamabe, H. Nakamura, H. Masutani, and J. Yodoi. (1994). Thiol-mediated redox regulation of lymphocyte proliferation. Possible involvement of adult T cell leukemia-derived factor and glutathione in transferrin receptor expression. J. Immunol. 152:5633–5642.
  • Koneru, M., D. Schaer, N. Monu, A. Ayala, Frey, A. B.. (2005). Defective proximal TCR signaling inhibits CD8+ tumor-infiltrating lymphocyte lytic function. J. Immunol. 174:1830–1840.
  • Kortylewski, M., M. Kujawski, T. Wang, S. Wei, S. Zhang, S. Pilon-Thomas, G. Niu, H. Kay, J. Mule, W. G. Kerr, R. Jove, D. Pardoll, Yu, H. (2005). Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat. Med. 11:1314–1321.
  • Kujawski, M., M. Kortylewski, H. Lee, A. Herrmann, H. Kay, Yu, H. (2008). Stat3 mediates myeloid cell-dependent tumor angiogenesis in mice. J. Clin. Invest. 118:3367–3377.
  • Kusmartsev, S., Gabrilovich, D. I. (2003). Inhibition of myeloid cell differentiation in cancer: the role of reactive oxygen species. J. Leukoc. Biol. 74:186–196.
  • Kusmartsev, S., Gabrilovich, D. I. (2005). STAT1 signaling regulates tumor-associated macrophage-mediated T cell deletion. J. Immunol. 174:4880–4891.
  • Kwidzinski, E., J. Bunse, O. Aktas, D. Richter, L. Mutlu, F. Zipp, R. Nitsch, Bechmann, I. (2005). Indolamine 2,3-dioxygenase is expressed in the CNS and down-regulates autoimmune inflammation. FASEB J. 19:1347–1349.
  • Levey, D., Srivastava, P. (1995). T cells from late tumor-bearing mice express normal levels of p56lck, p59fyn, ZAP-70 and CD3zeta despite suppressed cytolytic activity. J. Exp. Med. 182:1029–1036.
  • Li, H., Y. Han, Q. Guo, M. Zhang, Cao, X. (2009). Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-beta 1. J Immunol. 182:240–249.
  • Lin, E. Y., V. Gouon-Evans, A. V. Nguyen, Pollard, J. W. (2002). The macrophage growth factor CSF-1 in mammary gland development and tumor progression. J Mammary Gland Biol. Neoplasia 7:147–162.
  • Liu, C., Yu, S., J. Kappes, J. Wang, W. E. Grizzle, K. R. Zinn, Zhang, H. G. (2007). Expansion of spleen Myeloid-Derived Suppressor Cells represses NK cell cytotoxicity in tumor-bearing host. Blood 109:4336–4342.
  • Lob, S., A. Konigsrainer, H. G. Rammensee, G. Opelz, and P. Terness. (2009). Inhibitors of indoleamine-2,3-dioxygenase for cancer therapy: can we see the wood for the trees? Nat. Rev. Cancer 9:445–452.
  • Lob, S., A. Konigsrainer, D. Zieker, B. L. Brucher, H. G. Rammensee, G. Opelz, and P. Terness. (2009). IDO1 and IDO2 are expressed in human tumors: levo- but not dextro-1-methyl tryptophan inhibits tryptophan catabolism. Cancer Immunol. Immunother. 58:153–157.
  • Mansoor, M. A., A. M. Svardal, and P. M. Ueland. (1992). Determination of the in vivo redox status of cysteine, cysteinylglycine, homocysteine, and glutathione in human plasma. Anal. Biochem. 200:218–229.
  • Markiewski, M. M., R. A. DeAngelis, F. Benencia, S. K. Ricklin-Lichtsteiner, A. Koutoulaki, C. Gerard, G. Coukos, and J. D. Lambris. (2008). Modulation of the antitumor immune response by complement. Nat. Immunol. 9:1225–1235.
  • Mazzoni, A., V. Bronte, A. Visintin, J. H. Spitzer, E. Apolloni, P. Serafini, P. Zanovello, and D. M. Segal. (2002). Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism. J. Immunol. 168:689–695.
  • Menetrier-Caux, C., G. Montmain, M. C. Dieu, C. Bain, M. C. Favrot, C. Caux, Blay, J. Y. (1998). Inhibition of the differentiation of dendritic cells from CD34(+) progenitors by tumor cells: role of interleukin-6 and macrophage colony-stimulating factor. Blood 92:4778–4791.
  • Mirza, N., M. Fishman, I. Fricke, M. Dunn, A. M. Neuger, T. J. Frost, R. M. Lush, S. Antonia, Gabrilovich, D. I. (2006). All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients. Cancer Res. 66:9299–9307.
  • Monu, N., Frey, A. B. (2007). Suppression of proximal T cell receptor signaling and lytic function in CD8+ tumor-infiltrating T cells. Cancer Res. 67:11447–11454.
  • Movahedi, K., Guilliams, M., Van den Bossche, J., Van den Bergh, R., Gysemans, C., Beschin, A., De Baetselier, P., Van Ginderachter, J. A. (2008). Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity. Blood 111:4233–4244.
  • Munn, D. H. Mellor, A. L. (2004). IDO and tolerance to tumors. Trends Mol. Med. 10:15–18.
  • Munn, D. H., Mellor, A. L. (2007). Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J. Clin. Invest. 117:1147–1154.
  • Munn, D. H., Shafizadeh, E., Attwood, J. T., Bondarev, I., Pashine, A., Mellor, A. L. (1999). Inhibition of T cell proliferation by macrophage tryptophan catabolism. J. Exp. Med. 189:1363–1372.
  • Munn, D. H., Sharma, M. D., Lee, J. R., Jhaver, K. G., Johnson, T. S., Keskin, D. B>, Marshall, B., Chandler, P., Antonia, S. J., Burgess, R., Slingluff, Jr., C. L., Mellor, A. L. (2002). Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science 297:1867–1870.
  • Munn, D. H., Zhou, M., Attwood, J. T., Bondarev, I., Conway, S. J., Marshall, B., Brown, C., Mellor, A. L. (1998). Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 281:1191–1193.
  • Nagaraj, S., Gupta, K., Pisarev, V., Kinarsky, L., Sherman, S., Kang, L., Herber, D. L., Schneck, J., Gabrilovich, D. I. (2007). Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat. Med. 13:828–835.
  • Nagaraj, S., Schrum, A. G., Cho, H. I., Celis, E., Gabrilovich, D. I. (2010). Mechanism of T cell tolerance induced by myeloid-derived suppressor cells. J. Immunol. 184:3106–3116.
  • Nausch, N., Galani, I. E., Schlecker, E., Cerwenka, A. (2008). Mononuclear myeloid-derived “suppressor” cells express RAE-1 and activate natural killer cells. Blood 112:4080–4089.
  • Nefedova, Y., Cheng, P., Gilkes, D., Blaskovich, M., Beg, A. A., Sebti, S. M., Gabrilovich, D. I. (2005). Activation of dendritic cells via inhibition of Jak2/STAT3 signaling. J. Immunol. 175:4338–4346.
  • Nefedova, Y., Nagaraj, S., Rosenbauer, A., Muro-Cacho, C., Sebti, S. M., Gabrilovich, D. I. (2005). Regulation of dendritic cell differentiation and antitumor immune response in cancer by pharmacologic-selective inhibition of the janus-activated kinase 2/signal transducers and activators of transcription 3 pathway. Cancer Res. 65:9525–9535.
  • Norian, L. A., Rodriguez, P. C., O’Mara, L. A., Zabaleta, J., Ochoa, A. C., Cella, M., Allen, P. M. (2009). Tumor-infiltrating regulatory dendritic cells inhibit CD8+ T cell function via L-arginine metabolism. Cancer Res. 69:3086–3094.
  • Ochoa, A. C., Zea, A. H., Hernandez, C. Rodriguez, P. C. (2007). Arginase, prostaglandins, and myeloid-derived suppressor cells in renal cell carcinoma. Clin Cancer Res. 13:721s–726s.
  • Park, S. J., Nakagawa, T., Kitamura, H., Atsumi, T., Kamon, H., Sawa, S., Kamimura, D., Ueda, N., Iwakura, Y., Ishihara, K., Murakami, M., Hirano, T. (2004). IL-6 regulates in vivo dendritic cell differentiation through STAT3 activation. J. Immunol. 173:3844–3854.
  • Pekarek, L. A., Starr, B. A., Toledano, A. Y., Schreiber, H. (1995). Inhibition of tumor growth by elimination of granulocytes. J. Exp. Med. 181:435–440.
  • Radoja, S., Rao, T. D., Hillman, D., Frey, A. B. (2000). Mice bearing late-stage tumors have normal functional systemic T cell responses in vitro and in vivo. J. Immunol. 164:2619–2628.
  • Radoja, S., Saio, M., Schaer, D., Koneru, M., Vukmanovic, S., Frey, A. B. (2001). CD8(+) tumor-infiltrating T cells are deficient in perforin-mediated cytolytic activity due to defective microtubule-organizing center mobilization and lytic granule exocytosis. J. Immunol. 167:5042–5051.
  • Ravetch, J. V., Lanier, L. L. (2000). Immune inhibitory receptors. Science 290:84–89.
  • Rodriguez, P. C., Quiceno, D. G., Zabaleta, J., Ortiz, B., Zea, A. H., Piazuelo, M. B., Delgado, A., Correa, P., Brayer, J., Sotomayor, E. M., Antonia, S., Ochoa, J. B., Ochoa, A. C. (2004). Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res. 64:5839–5849.
  • Rosenberg, S. A., Yang, J. C., Restifo, N. P. (2004). Cancer immunotherapy: moving beyond current vaccines. Nat. Med. 10:909–915.
  • Saio, M., Radoja, S., Marino, M., Frey, A. B. (2001). Tumor-infiltrating macrophages induce apoptosis in activated CD8(+) T cells by a mechanism requiring cell contact and mediated by both the cell-associated form of TNF and nitric oxide. J. Immunol. 167:5583–5593.
  • Salvadori, S., Martinelli, G., Zier, K. (2000). Resection of solid tumors reverses T cell defects and restores protective immunity. J. Immunol. 164:2214–2220.
  • Schmielau, J., Finn, O. J. (2001). Activated granulocytes and granulocyte-derived hydrogen peroxide are the underlying mechanism of suppression of t-cell function in advanced cancer patients. Cancer Res. 61:4756–4760.
  • Serafini, P., De Santo, C., Marigo, I., Cingarlini, S., Dolcetti, L., Gallina, G., Zanovello, P., Bronte, V. (2004). Derangement of immune responses by myeloid suppressor cells. Cancer Immunol. Immunother. 53:64–72.
  • Shojaei, F., Ferrara, N. (2008). Refractoriness to antivascular endothelial growth factor treatment: role of myeloid cells. Cancer Res. 68:5501–5504.
  • Shojaei, F., Wu, X., Qu, X., Kowanetz, M., Yu, L., Tan, M., Meng, Y. G., Ferrara, N. (2009). G-CSF-initiated myeloid cell mobilization and angiogenesis mediate tumor refractoriness to anti-VEGF therapy in mouse models. Proc. Natl. Acad. Sci. U S A 106:6742–6747.
  • Shojaei, F., Wu, X., Zhong, C. Yu, L.,Liang, X. H., Yao, J., Blanchard, D., Bais, C.,Peale, F. V., van Bruggen, N., Ho, C., Ross, J., Tan, M., Carano, R. A., Meng, Y. G., Ferrara, N. (2007). Bv8 regulates myeloid-cell-dependent tumour angiogenesis. Nature 450:825–831.
  • Sica, A., Bronte, V. (2007). Altered macrophage differentiation and immune dysfunction in tumor development. J. Clin. Invest. 117:1155–1166.
  • Sinha, P., Clements, V. K., Bunt, S. K., Albelda, S. M., Ostrand-Rosenberg, S. (2007). Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J. Immunol. 179:977–983.
  • Sinha, P., Clements, V. K., Miller, S., Ostrand-Rosenberg, S. (2005a). Tumor immunity: a balancing act between T cell activation, macrophage activation and tumor-induced immune suppression. Cancer Immunol. Immunother. 54:1137–1142.
  • Sinha, P., Clements, V. K., Ostrand-Rosenberg, S. (2005b). Interleukin-13-regulated M2 macrophages in combination with Myeloid-Derived Suppressor Cells block immune surveillance against metastasis. Cancer Res. 65:11743–11751.
  • Sinha, P., Clements, V. K., Ostrand-Rosenberg, S. (2005). Reduction of myeloid-derived suppressor cells and induction of M1 macrophages facilitate the rejection of established metastatic disease. J. Immunol. 174:636–645.
  • Sinha, P., Okoro, C., Foell, D., Freeze, H. H., Ostrand-Rosenberg, S., Srikrishna, G. (2008). Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells. J. Immunol. 181:4666–4675.
  • Srivastava, M. K., Sinha, P., Clements, V. K., Rodriguez, P., Ostrand-Rosenberg, S. (2010). Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine. Cancer Res. 70:68–77.
  • Steinbrink, K., Graulich, E., Kubsch, S., Knop, J., Enk, A. H. (2002). CD4(+) and CD8(+) anergic T cells induced by interleukin-10-treated human dendritic cells display antigen-specific suppressor activity. Blood 99:2468–2476.
  • Strober, S. (1984). Natural suppressor (NS) cells, neonatal tolerance, and total lymphoid irradiation: exploring obscure relationships. Annu. Rev. Immunol. 2:219–237.
  • Suzuki, E., Kapoor, V., Jassar, A. S., Kaiser, L. R., Albelda, S. M. (2005). Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ Myeloid-Derived Suppressor Cells in tumor-bearing animals and enhances antitumor immune activity. Clin. Cancer Res. 11:6713–6721.
  • Taylor, M. W., Feng, G. S. (1991). Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. FASEB J. 5:2516–2522.
  • Terabe, M., Matsui, S., Park, J. M., Mamura, M., Noben-Trauth, N., Donaldson, D. D., Chen, W., Wahl, S. W., Ledbetter, S., Pratt, B., Letterio, J. J., Paul, W. E., Berzofsky, J. A. (2003). Transforming growth factor-beta production and myeloid cells are an effector mechanism through which CD1d-restricted T cells block cytotoxic T lymphocyte-mediated tumor immunosurveillance: abrogation prevents tumor recurrence. J. Exp. Med. 198:1741–1752.
  • Turovskaya, O., Foell, D., Sinha, P., Vogl, T., Newlin, R., Nayak, J., Nguyen, M., Olsson, A., Nawroth, P. P., Bierhaus, A., Varki, N., Kronenberg, M., Freeze, H. H., Srikrishna, G. (2008). RAGE, carboxylated glycans and S100A8/A9 play essential roles in colitis-associated carcinogenesis. Carcinogenesis 29:2035–2043.
  • Uyttenhove, C., Pilotte, L., Theate, I., Stroobant, V., Colau, D., Parmentier, N., Boon, T., Van den Eynde, B. J. (2003). Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat. Med. 9:1269–1274.
  • Watanabe, S., Deguchi, K., Zheng, R., Tamai, H., Wang, L. X., Cohen, P. A., Shu, S. (2008). Tumor-induced CD11b+Gr-1+ myeloid cells suppress T cell sensitization in tumor-draining lymph nodes. J. Immunol. 181:3291–3300.
  • Wu, G., Morris, Jr., S. M. (1998). Arginine metabolism: nitric oxide and beyond. Biochem. J. 336 (Pt 1):1–17.
  • Xu, W., Liu, L. Z., Loizidou, M., Ahmed, M., Charles, I. G. (2002). The role of nitric oxide in cancer. Cell Res. 12:311–320.
  • Yang, L., DeBusk, L. M., Fukuda, K., Fingleton, B., Green-Jarvis, B., Shyr, Y., Matrisian, L. R., Carbone, D. P., Lin, P. C. (2004). Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell 6:409–421.
  • Youn, J. I., Nagaraj, S., Collazo, M., Gabrilovich, D. I. (2008). Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J. Immunol. 181:5791–5802.
  • Zhou, Z., French, D. L., Ma, G., Eisenstein, S., Chen, Y., Divino, C.M., Keller, G., Chen, S. H., Pan, P. Y. (2010). Development and function of myeloid-derived suppressor cells generated from mouse embryonic and hematopoietic stem cells. Stem Cells 28:620–632.

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