The combination of a novel immunomodulator with a regulatory T cell suppressing antibody (DTA-1) regress advanced stage B16F10 solid tumor by repolarizing tumor associated macrophages in situ

References

• Bahirwani R, Reddy KR. Drug-induced liver injury due to cancer chemotherapeutic agents. Semin Liver Dis 2014; 34:162-71; PMID:24879981; http://dx.doi.org/10.1055/s-0034-1375957
   PubMed Web of Science ®Google Scholar
• Shaikh AY, Shih JA. Chemotherapy-induced cardiotoxicity. Curr Heart Fail Rep 2012; 9:117-27; PMID:22382639; http://dx.doi.org/10.1007/s11897-012-0083-y
   PubMedGoogle Scholar
• François S, Bensidhoum M, Mouiseddine M, Mazurier C, Allenet B, Semont A, Frick J, Saché A, Bouchet S, Thierry D et al. Local irradiation not only induces homing of human mesenchymal stem cells at exposed sites but promotes their widespread engraftment to multiple organs: a study of their quantitative distribution after irradiation damage. Stem Cells 2006; 24:1020-9; PMID:16339642; http://dx.doi.org/10.1634/stemcells.2005-0260
   PubMed Web of Science ®Google Scholar
• Bacac M, Stamenkovic I. Metastatic cancer cell. Annu Rev Pathol 2008; 3:221-47; PMID:18233952; http://dx.doi.org/10.1146/annurev.pathmechdis.3.121806.151523
   PubMed Web of Science ®Google Scholar
• Lizée G, Overwijk WW, Radvanyi L, Gao J, Sharma P, Hwu P. Harnessing the power of the immune system to target cancer. Annu Rev Med 2013; 64:71-90; PMID:23092383; http://dx.doi.org/10.1146/annurev-med-112311-083918
   PubMed Web of Science ®Google Scholar
• Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med 2013; 19:1423-37; PMID:24202395; http://dx.doi.org/10.1038/nm.3394
   PubMed Web of Science ®Google Scholar
• Flavell RA, Sanjabi S, Wrzesinski SH, Licona-Limón P. The polarization of immune cells in the tumour environment by TGFbeta. Nat Rev Immunol 2010; 10:554-67; PMID:20616810; http://dx.doi.org/10.1038/nri2808
   PubMed Web of Science ®Google Scholar
• Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 2004; 4:71-8; PMID:14708027; http://dx.doi.org/10.1038/nrc1256
   PubMed Web of Science ®Google Scholar
• Mougiakakos D, Choudhury A, Lladser A, Kiessling R, Johansson CC. Regulatory T cells in cancer. Adv Cancer Res 2010; 107:57-117; PMID:20399961; http://dx.doi.org/10.1016/S0065-230X(10)07003-X
   PubMed Web of Science ®Google Scholar
• Takaishi K, Komohara Y, Tashiro H, Ohtake H, Nakagawa T, Katabuchi H, Takeya M. Involvement of M2-polarized macrophages in the ascites from advanced epithelial ovarian carcinoma in tumor progression via Stat3 activation. Cancer Sci 2010; 101:2128-36; PMID:20860602; http://dx.doi.org/10.1111/j.1349-7006.2010.01652.x
   PubMed Web of Science ®Google Scholar
• Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR, Kaiser EA, Snyder LA, Pollard JW. CCL2 recruits inflammatory monocytes to facilitate breast-tumourmetastasis. Nature 2011; 475:222-5; PMID:21654748; http://dx.doi.org/10.1038/nature10138
   PubMed Web of Science ®Google Scholar
• Mantovani A, Sozzani S, Locati M, Allavena P, Sica A. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 2002; 23:549-55; PMID:12401408; http://dx.doi.org/10.1016/S1471-4906(02)02302-5
   PubMed Web of Science ®Google Scholar
• Sica A, Saccani A, Bottazzi B, Polentarutti N, Vecchi A, van Damme J, Mantovani A. Autocrine production of IL-10 mediates defective IL-12 production and NF-kappa B activation in tumor-associated macrophages. J Immunol 2000; 164:762-67; PMID:10623821; http://dx.doi.org/10.4049/jimmunol.164.2.762
   PubMed Web of Science ®Google Scholar
• Lamagna C, Aurrand-Lions M, Imhof BA. Dual role of macrophages in tumor growth and angiogenesis. J Leukoc Biol 2006; 80:705-13; PMID:16864600; http://dx.doi.org/10.1189/jlb.1105656
   PubMed Web of Science ®Google Scholar
• Schoppmann SF, Birner P, Stöckl J, Kalt R, Ullrich R, Caucig C, Kriehuber E, Nagy K, Alitalo K, Kerjaschki D. Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis. Am J Pathol 2002; 161:947-56; PMID:12213723; http://dx.doi.org/10.1016/S0002-9440(10)64255-1
   PubMed Web of Science ®Google Scholar
• Jinushi M, Chiba S, Yoshiyama H, Masutomi K, Kinoshita I, Dosaka-Akita H, Yagita H, Takaoka A, Tahara H. Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells. Proc Natl Acad Sci USA 2011; 108:12425-30; PMID:21746895; http://dx.doi.org/10.1073/pnas.1106645108
   PubMed Web of Science ®Google Scholar
• Su S, Liu Q, Chen J, Chen J, Chen F, He C, Huang D, Wu W, Lin L, Huang W et al. A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis. Cancer Cell 2014; 25:605-20; PMID:24823638; http://dx.doi.org/10.1016/j.ccr.2014.03.021
   PubMed Web of Science ®Google Scholar
• Lepique AP, Daghastanli KR, Cuccovia IM, Villa LL. HPV16 tumor associated macrophages suppress antitumor T cell responses. Clin Cancer Res 2009; 15:4391-400; PMID:19549768; http://dx.doi.org/10.1158/1078-0432.CCR-09-0489
   PubMed Web of Science ®Google Scholar
• Liu J, Zhang N, Li Q, Zhang W, Ke F, Leng Q, Wang H, Chen J, Wang H. Tumor-associated macrophages recruit CCR6+ regulatory T cells and promote the development of colorectal cancer via enhancing CCL20 production in mice. PLOS ONE 2011; 6: e19495; PMID:21559338; http://dx.doi.org/10.1371/journal.pone.0019495
   PubMed Web of Science ®Google Scholar
• Li X, Kostareli E, Suffner J, Garbi N, Hämmerling GJ. Efficient Regulatory T cell depletion induces T-cell infiltration and rejection of large tumors. Eur J Immunol 2010; 40:3325-35; PMID:21072887; http://dx.doi.org/10.1002/eji.201041093
   PubMed Web of Science ®Google Scholar
• Schlecker E, Stojanovic A, Eisen C, Quack C, Falk CS, Umansky V, Cerwenka A. Tumor-infiltrating monocytic myeloid-derived suppressor cells mediate CCR5-dependent recruitment of regulatory T cells favoring tumor growth. J Immunol 2012; 189:5602-11; PMID:23152559; http://dx.doi.org/10.4049/jimmunol.1201018
   PubMed Web of Science ®Google Scholar
• Facciabene A, Motz GT, Coukos G. T-regulatory cells: key players in tumor immune escape and angiogenesis. Cancer Res 2012; 72:2162-71; PMID:22549946; http://dx.doi.org/10.1158/0008-5472.CAN-11-3687
   PubMed Web of Science ®Google Scholar
• Adhikari A, Gupta G, Majumder S, Banerjee S, Bhattacharjee S, Bhattacharya P, Kumari S, Haldar S, Majumdar SB, Saha B et al. Mycobacterium indicus pranii (Mw) re-establishes host protective immune response in Leishmania donovani infected macrophages: critical role of IL-12. PLOS ONE 2012; 7: e40265
   PubMed Web of Science ®Google Scholar
• Adhikari A, Majumder S, Banerjee S, Gupta G, Bhattacharya P, Majumdar SB, Saha B, Majumdar S. Mycobacterium indicus pranii (Mw) mediated protection against visceral leishmaniasis: involvement of TLR4 signalling. J Antimicrob Chemother 2012; 67:2892-902; PMID:22879460
   PubMed Web of Science ®Google Scholar
• Rakshit S, Ponnusamy M, Papanna S, Saha B, Ahmed A, Nandi D. Immunotherapeutic efficacy of Mycobacterium indicus pranii in eliciting anti-tumor T cell responses: critical roles of IFN-γ. Int J Cancer 2012; 130:865-75; PMID:21455983; http://dx.doi.org/10.1002/ijc.26099
   PubMed Web of Science ®Google Scholar
• Saccani A, Schioppa T, Porta C, Biswas SK, Nebuloni M, Vago L, Bottazzi B, Colombo MP, Mantovani A, Sica A. p50 nuclear factor-kappa B overexpression in tumor-associated macrophages inhibits M1 inflammatory responses and antitumorresistance. Cancer Res 2006; 66:11432-40; PMID:17145890; http://dx.doi.org/10.1158/0008-5472.CAN-06-1867
   PubMed Web of Science ®Google Scholar
• Soki FN, Koh AJ, Jones JD, Kim YW, Dai J, Keller ET, Pienta KJ, Atabai K, Roca H, McCauley LK. Polarization of prostate cancer associated macrophages is inducedby milk-fat globule-EGF factor 8 (MFG-E8) mediated efferocytosis. J BiolChem 2014; 289:24560-72 [Epub ahead of print]; PMID: 25006249; http://dx.doi.org/10.1074/jbc.M114.571620
   PubMed Web of Science ®Google Scholar
• Cederbom L, Hall H, Ivars F. CD4+CD25+ regulatory T cells down-regulateco-stimulatory molecules on antigen-presenting cells. Eur J Immunol 2000; 30:1538-43; PMID:10898488; http://dx.doi.org/10.1002/1521-4141(200006)30:6%3c1538::AID-IMMU1538%3e3.0.CO;2-X
   PubMed Web of Science ®Google Scholar
• André S, Tough DF, Lacroix-Desmazes S, Kaveri SV, Bayry J. Surveillance of antigen-presenting cells by CD4+ CD25+ regulatory T cells in autoimmunity: immunopathogenesis and therapeutic implications. Am J Pathol 2009; 174:1575-87; PMID:19349365; http://dx.doi.org/10.2353/ajpath.2009.080987
   PubMed Web of Science ®Google Scholar
• Taylor A, Verhagen J, Blaser K, Akdis M, Akdis CA. Mechanisms of immunesuppression by interleukin-10 and transforming growth factor-beta: 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
   PubMed Web of Science ®Google Scholar
• Kortylewski M, Xin H, Kujawski M, Lee H, Liu Y, Harris T, Drake C, Pardoll D, Yu H. Regulation of the IL-23 and IL-12 balance by Stat3 signaling in the tumor microenvironment. Cancer Cell 2009; 15:114-23; PMID:19185846; http://dx.doi.org/10.1016/j.ccr.2008.12.018
   PubMed Web of Science ®Google Scholar
• Turk MJ, Guevara-Patiño JA, Rizzuto GA, Engelhorn ME, Sakaguchi S, Houghton AN. Concomitant tumor immunity to a poorly immunogenic melanoma is prevented by regulatory T cells. J Exp Med 2004; 200:771-82; PMID:15381730; http://dx.doi.org/10.1084/jem.20041130
   PubMed Web of Science ®Google Scholar
• Duff MD, Mestre J, Maddali S, Yan ZP, Stapleton P, Daly JM. Analysis of gene expression in the tumor-associated macrophage. J Surg Res 2007; 142:119-28; PMID:17597158; http://dx.doi.org/10.1016/j.jss.2006.12.542
   PubMed Web of Science ®Google Scholar
• Banerjee S, Halder K, Bose A, Bhattacharya P, Gupta G, Karmahapatra S, Das S, Chaudhuri S, Bhattacharyya Majumdar S, Majumdar S. TLR signaling-mediated differential histone modification at IL-10 and IL-12 promoter region leads to functional impairments in tumor-associated macrophages. Carcinogenesis 2011; 32:1789-97; PMID:21926109; http://dx.doi.org/10.1093/carcin/bgr208
   PubMed Web of Science ®Google Scholar
• Fahey TJ, Tracey KJ, Tekamp-Olson P, Cousens LS, Jones WG, Shire GT, Cerami A, Sherry B. Macrophage inflammatory protein 1 modulates macrophage function. J Immunol 1992; 148:2764-9; PMID:1573267
   PubMed Web of Science ®Google Scholar
• Majumdar S, Kane LH, Rossi MW, Volpp BD, Nauseef WM, Korchak HM. Protein kinase C isotypes and signal-transduction in human neutrophils: selective substrate specificity of calcium-dependent beta-PKC and novel calcium-independent nPKC. Biochim Biophys Acta 1993; 1176:276-86; PMID:8471629; http://dx.doi.org/10.1016/0167-4889(93)90056-U
   PubMed Web of Science ®Google Scholar
• Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 1979; 76:4350-4; PMID:388439
   PubMed Web of Science ®Google Scholar
• Ghosh J, Das S, Guha R, Ghosh D, Naskar K, Das A, Roy S. Hyperlipidemia offers protection against Leishmania donovani infection: role of membrane cholesterol. J Lipid Res 2012; 53:2560-72; PMID:23060454; http://dx.doi.org/10.1194/jlr.M026914
   PubMed Web of Science ®Google Scholar
• Bose A, Taylor JL, Alber S, Watkins SC, Garcia JA, Rini BI, Ko JS, Cohen PA, Finke JH, Storkus WJ. Sunitinib facilitates the activation and recruitment of therapeutic anti-tumor immunity in concert with specific vaccination. Int J Cancer 2011; 129:2158-70; PMID:21170961; http://dx.doi.org/10.1002/ijc.25863
   PubMed Web of Science ®Google Scholar
• Bose A, Barik S, Banerjee S, Ghosh T, Mallick A, Bhattacharyya Majumdar S, Goswami KK, Bhuniya A, Banerjee S, Baral R et al. Tumor-derived vascular pericytes anergize Th cells. J Immunol 2013; 191:971-81; PMID:23785117; http://dx.doi.org/10.4049/jimmunol.1300280
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 1982; 126:131-8; PMID:7181105; http://dx.doi.org/10.1016/0003-2697(82)90118-X
   PubMed Web of Science ®Google Scholar
• Zhao X, Bose A, Komita H, Taylor JL, Kawabe M, Chi N, Spokas L, Lowe DB, Goldbach C, Alber S. Intratumoral IL-12 gene therapy results in the crosspriming of Tc1 cells reactive against tumor-associated stromal antigens. Mol. Ther 2011; 19:805-14; PMID:21189473; http://dx.doi.org/10.1038/mt.2010.295
   PubMed Web of Science ®Google Scholar