Emerging strategies for cancer immunoprevention

Oncogene

Volumn 34, Issue 50, 2015, Pages 6029-6039

  Roeser, J C ^a   Leach, S D ^b   McAllister, F ^c  

^a JOHNS HOPKINS UNIVERSITY   (United States)

^b MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^c UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERFERON; CANCER VACCINE; CD4 ANTIGEN; CD8 ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; INTERLEUKIN 1; INTERLEUKIN 17; INTERLEUKIN 6; INTERLEUKIN 8; PROGRAMMED DEATH 1 LIGAND 1; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; PDCD1 PROTEIN, HUMAN; PROGRAMMED DEATH 1 RECEPTOR; STAT3 PROTEIN;

CANCER IMMUNOTHERAPY; CANCER INCIDENCE; CANCER PREVENTION; CANCER RISK; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; HUMAN; IMMUNE SYSTEM; IMMUNOSURVEILLANCE; LYMPHOID CELL; MACROPHAGE; MAST CELL; NATURAL KILLER T CELL; NEOPLASM; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; ANTAGONISTS AND INHIBITORS; CHEMOPROPHYLAXIS; DENDRITIC CELL; IMMUNOLOGICAL MONITORING; IMMUNOLOGY; IMMUNOTHERAPY; NEOPLASMS; PHYSIOLOGY; TH17 CELL;

CHEMOPREVENTION; DENDRITIC CELLS; HUMANS; IMMUNOTHERAPY; INTERLEUKIN 1 RECEPTOR ANTAGONIST PROTEIN; INTERLEUKIN-6; INTERLEUKIN-8; MONITORING, IMMUNOLOGIC; NEOPLASMS; PROGRAMMED CELL DEATH 1 RECEPTOR; STAT3 TRANSCRIPTION FACTOR; T-LYMPHOCYTES, REGULATORY; TH17 CELLS;

EID: 84949624502     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2015.98     Document Type: Review

References (190)

1. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Eng J Med 2010; 363: 411-422.
2. Spratt JS. The primary and secondary prevention of cancer. J Surg Oncol 1981; 18: 219-230.
3. Patterson SL, Colbert Maresso K, Hawk E. Cancer chemoprevention: successes and failures. Clin Chem 2013; 59: 94-101.
4. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998; 90: 1371-1388.
5. Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Cecchini RS, Atkins JN et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 2006; 295: 2727-2741.
6. Phillips RK, Wallace MH, Lynch PM, Hawk E, Gordon GB, Saunders BP et al. A randomised, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis. Gut 2002; 50: 857-860.
7. Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Eng J Med 2000; 342: 1946-1952.
8. Steinberg G, Bahnson R, Brosman S, Middleton R, Wajsman Z, Wehle M. Efficacy and safety of valrubicin for the treatment of Bacillus Calmette-Guerin refractory carcinoma in situ of the bladder. The Valrubicin Study Group. The Journal of urology 2000; 163: 761-767.
9. Sylvester RJ. Bacillus Calmette-Guerin treatment of non-muscle invasive bladder cancer. Int J Urol 2011; 18: 113-120.
10. Lebwohl M, Swanson N, Anderson LL, Melgaard A, Xu Z, Berman B. Ingenol mebutate gel for actinic keratosis. N Eng J Med 2012; 366: 1010-1019.
11. Pardoll DM. Spinning molecular immunology into successful immunotherapy. Nat Rev Immunol 2002; 2: 227-238.
12. Pardoll DM. Immunology beats cancer: a blueprint for successful translation. Nat Immunol 2012; 13: 1129-1132.
13. Chang MH, Chen CJ, Lai MS, Hsu HM, Wu TC, Kong MS et al. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N Eng J Med 1997; 336: 1855-1859.
14. Gwack J, Park SK, Lee EH, Park B, Choi Y, Yoo KY. Hepatitis B vaccination and liver cancer mortality reduction in Korean children and adolescents. Asian Pac J Cancer Prev 2011; 12: 2205-2208.
15. CDC. Vaccine information statement: HPV (human papillomavirus) vaccine http://wwwcdcgovezproxywelchjhmiedu/vaccines/pubs/vis/downloads/vis-hpvgardasilpdf.
16. Olive KP, Tuveson DA. The use of targeted mouse models for preclinical testing of novel cancer therapeutics. Clin Cancer Res 2006; 12: 5277-5287.
17. Stutman O. Tumor development after 3-methylcholanthrene in immunologically deficient athymic-nude mice. Science 1974; 183: 534-536.
18. Dighe AS, Richards E, Old LJ, Schreiber RD. Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN gamma receptors. Immunity 1994; 1: 447-456.
19. Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ et al. Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci USA 1998; 95: 7556-7561.
20. van den Broek ME, Kagi D, Ossendorp F, Toes R, Vamvakas S, Lutz WK et al. Decreased tumor surveillance in perforin-deficient mice. J Exp Med 1996; 184: 1781-1790.
21. Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ et al. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 2001; 410: 1107-1111.
22. Shinkai Y, Rathbun G, Lam KP, Oltz EM, Stewart V, Mendelsohn M et al. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 1992; 68: 855-867.
23. Teng MW, Swann JB, Koebel CM, Schreiber RD, Smyth MJ. Immune-mediated dormancy: an equilibrium with cancer. J Leukoc Biol 2008; 84: 988-993.
24. Sheil AG. Cancer after transplantation. World J Surg 1986; 10: 389-396.
25. Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol 2004; 22: 329-360.
26. Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 2002; 3: 991-998.
27. Becker JC, Andersen MH, Schrama D, Thor Straten P. Immune-suppressive properties of the tumor microenvironment. Cancer Immunol Immunother 2013; 62: 1137-1148.
28. Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat Med 2004; 10: 909-915.
29. Murdaca G, Spano F, Contatore M, Guastalla A, Penza E, Magnani O et al. Infection risk associated with anti-TNF-alpha agents: a review. Expert opinion on drug safety 2015; 14: 571-582.
30. Gogas H, Ioannovich J, Dafni U, Stavropoulou-Giokas C, Frangia K, Tsoutsos D et al. Prognostic significance of autoimmunity during treatment of melanoma with interferon. N Eng J Med 2006; 354: 709-718.
31. Solomon SD, Pfeffer MA, McMurray JJ, Fowler R, Finn P, Levin B et al. Effect of celecoxib on cardiovascular events and blood pressure in two trials for the prevention of colorectal adenomas. Circulation 2006; 114: 1028-1035.
32. Heinrich PC, Behrmann I, Haan S, Hermanns HM, Muller-Newen G, Schaper F. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 2003; 374: 1-20.
33. Jones SA, Richards PJ, Scheller J, Rose-John S. IL-6 transsignaling: the in vivo consequences. J Interferon Cytokine Res 2005; 25: 241-253.
34. Nowell MA, Williams AS, Carty SA, Scheller J, Hayes AJ, Jones GW et al. Therapeutic targeting of IL-6 trans signaling counteracts STAT3 control of experimental inflammatory arthritis. J Immunol 2009; 182: 613-622.
35. Sansone P, Storci G, Tavolari S, Guarnieri T, Giovannini C, Taffurelli M et al. IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. J Clin Invest 2007; 117: 3988-4002.
36. Gao SP, Mark KG, Leslie K, Pao W, Motoi N, Gerald WL et al. Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas. J Clin Invest 2007; 117: 3846-3856.
37. Lesina M, Kurkowski MU, Ludes K, Rose-John S, Treiber M, Kloppel G et al. Stat3/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer. Cancer Cell 2011; 19: 456-469.
38. Becker C, Fantini MC, Schramm C, Lehr HA, Wirtz S, Nikolaev A et al. TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity 2004; 21: 491-501.
39. Grivennikov S, Karin E, Terzic J, Mucida D, Yu GY, Vallabhapurapu S et al. IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell 2009; 15: 103-113.
40. Nishimoto N, Kanakura Y, Aozasa K, Johkoh T, Nakamura M, Nakano S et al. Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease. Blood 2005; 106: 2627-2632.
41. Kurzrock R, Voorhees PM, Casper C, Furman RR, Fayad L, Lonial S et al. A phase I, open-label study of siltuximab, an anti-IL-6 monoclonal antibody, in patients with B-cell non-Hodgkin lymphoma, multiple myeloma, or Castleman disease. Clin Cancer Res 2013; 19: 3659-3670.
42. Zhang Y, Yan W, Collins MA, Bednar F, Rakshit S, Zetter BR et al. Interleukin-6 is required for pancreatic cancer progression by promoting MAPK signaling activation and oxidative stress resistance. Cancer Res 2013; 73: 6359-6374.
43. Holmes WE, Lee J, Kuang WJ, Rice GC, Wood WI. Structure and functional expression of a human interleukin-8 receptor. Science 1991; 253: 1278-1280.
44. Murphy PM, Tiffany HL. Cloning of complementary DNA encoding a functional human interleukin-8 receptor. Science 1991; 253: 1280-1283.
45. Huang S, Mills L, Mian B, Tellez C, McCarty M, Yang XD et al. Fully humanized neutralizing antibodies to interleukin-8 (ABX-IL8) inhibit angiogenesis, tumor growth, and metastasis of human melanoma. Am J Pathol 2002; 161: 125-134.
46. Mian BM, Dinney CP, Bermejo CE, Sweeney P, Tellez C, Yang XD et al. Fully human anti-interleukin 8 antibody inhibits tumor growth in orthotopic bladder cancer xenografts via down-regulation of matrix metalloproteases and nuclear factor-kappaB. Clin Cancer Res 2003; 9: 3167-3175.
47. Yao C, Lin Y, Chua MS, Ye CS, Bi J, Li W et al. Interleukin-8 modulates growth and invasiveness of estrogen receptor-negative breast cancer cells. Int J Cancer 2007; 121: 1949-1957.
48. Merritt WM, Lin YG, Spannuth WA, Fletcher MS, Kamat AA, Han LY et al. Effect of interleukin-8 gene silencing with liposome-encapsulated small interfering RNA on ovarian cancer cell growth. J Natl Cancer Inst 2008; 100: 359-372.
49. Dwyer MP, Yu Y, Chao J, Aki C, Chao J, Biju P et al. Discovery of 2-hydroxy-N, N-dimethyl-3-{2-[[(R)-1-(5-methylfuran-2-yl)propyl]amino]-3,4-dioxocyclobut-1-enylamino}benzamide (SCH 527123): a potent, orally bioavailable CXCR2/CXCR1 receptor antagonist. J Med Chem 2006; 49: 7603-7606.
50. Gonsiorek W, Fan X, Hesk D, Fossetta J, Qiu H, Jakway J et al. Pharmacological characterization of Sch527123, a potent allosteric CXCR1/CXCR2 antagonist. J Pharmacol Exp Ther 2007; 322: 477-485.
51. Lai G, Merritt JR, He Z, Feng D, Chao J, Czarniecki MF et al. Synthesis and structure-activity relationships of new disubstituted phenyl-containing 3,4-diamino-3-cyclobutene-1,2-diones as CXCR2 receptor antagonists. Bioorg Med Chem Lett 2008; 18: 1864-1868.
52. McCleland BW, Davis RS, Palovich MR, Widdowson KL, Werner ML, Burman M et al. Comparison of N,N′-diarylsquaramides and N,N′-diarylureas as antagonists of the CXCR2 chemokine receptor. Bioorg Med Chem Lett 2007; 17: 1713-1717.
53. Ning Y, Labonte MJ, Zhang W, Bohanes PO, Gerger A, Yang D et al. The CXCR2 antagonist, SCH-527123, shows antitumor activity and sensitizes cells to oxaliplatin in preclinical colon cancer models. Mol Cancer Ther 2012; 11: 1353-1364.
54. Walters I, Austin C, Austin R, Bonnert R, Cage P, Christie M et al. Evaluation of a series of bicyclic CXCR2 antagonists. Bioorg Med Chem Lett 2008; 18: 798-803.
55. Winters MP, Crysler C, Subasinghe N, Ryan D, Leong L, Zhao S et al. Carboxylic acid bioisosteres acylsulfonamides, acylsulfamides, and sulfonylureas as novel antagonists of the CXCR2 receptor. Bioorg Med Chem Lett 2008; 18: 1926-1930.
56. Miossec P, Kolls JK. Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov 2012; 11: 763-776.
57. Weaver CT, Hatton RD, Mangan PR, Harrington LE. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol 2007; 25: 821-852.
58. Rachitskaya AV, Hansen AM, Horai R, Li Z, Villasmil R, Luger D et al. Cutting edge: NKT cells constitutively express IL-23 receptor and RORgammat and rapidly produce IL-17 upon receptor ligation in an IL-6-independent fashion. J Immunol 2008; 180: 5167-5171.
59. Do JS, Fink PJ, Li L, Spolski R, Robinson J, Leonard WJ et al. Cutting edge: spontaneous development of IL-17-producing gamma delta T cells in the thymus occurs via a TGF-beta 1-dependent mechanism. J Immunol 2010; 184: 1675-1679.
60. Ciric B, El-behi M, Cabrera R, Zhang GX, Rostami A. IL-23 drives pathogenic IL-17-producing CD8+ T cells. J Immunol 2009; 182: 5296-5305.
61. Toy D, Kugler D, Wolfson M, Vanden Bos T, Gurgel J, Derry J et al. Cutting edge: interleukin 17 signals through a heteromeric receptor complex. J Immunol 2006; 177: 36-39.
62. McGeachy MJ, Bak-Jensen KS, Chen Y, Tato CM, Blumenschein W, McClanahan T et al. TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol 2007; 8: 1390-1397.
63. Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 2003; 278: 1910-1914.
64. Yang XO, Panopoulos AD, Nurieva R, Chang SH, Wang D, Watowich SS et al. STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem 2007; 282: 9358-9363.
65. McAllister F. Oncogenic Kras activates a hematopoietic-to-epithelial IL-17 signaling axis in preinvasive pancreatic neoplasia. Cancer Cell 2014; 25: 621-637.
66. Wagsater D, Lofgren S, Hugander A, Dimberg J. Expression of interleukin-17 in human colorectal cancer. Anticancer Res 2006; 26: 4213-4216.
67. Chae WJ, Gibson TF, Zelterman D, Hao L, Henegariu O, Bothwell AL. Ablation of IL-17A abrogates progression of spontaneous intestinal tumorigenesis. Proc Natl Acad Sci USA 2010; 107: 5540-5544.
68. Hyun YS, Han DS, Lee AR, Eun CS, Youn J, Kim HY. Role of IL-17A in the development of colitis-associated cancer. Carcinogenesis 2012; 33: 931-936.
69. Nam JS, Terabe M, Kang MJ, Chae H, Voong N, Yang YA et al. Transforming growth factor beta subverts the immune system into directly promoting tumor growth through interleukin-17. Cancer Res 2008; 68: 3915-3923.
70. Numasaki M, Fukushi J, Ono M, Narula SK, Zavodny PJ, Kudo T et al. Interleukin-17 promotes angiogenesis and tumor growth. Blood 2003; 101: 2620-2627.
71. Wang L, Yi T, Kortylewski M, Pardoll DM, Zeng D, Yu H. IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med 2009; 206: 1457-1464.
72. Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen HR et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med 2009; 15: 1016-1022.
73. Muranski P, Boni A, Antony PA, Cassard L, Irvine KR, Kaiser A et al. Tumor-specific Th17-polarized cells eradicate large established melanoma. Blood 2008; 112: 362-373.
74. Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang Y et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet 2008; 371: 1665-1674.
75. Hueber W, Patel DD, Dryja T, Wright AM, Koroleva I, Bruin G et al. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med 2010; 2: 52ra72.
76. Leonardi C, Matheson R, Zachariae C, Cameron G, Li L, Edson-Heredia E et al. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Eng J Med 2012; 366: 1190-1199.
77. Papp KA, Leonardi C, Menter A, Ortonne JP, Krueger JG, Kricorian G et al. Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. N Eng J Med 2012; 366: 1181-1189.
78. Hemdan NY. Anti-cancer versus cancer-promoting effects of the interleukin-17-producing T helper cells. Immunol Lett 2013; 149: 123-133.
79. Martin-Orozco N, Dong C. The IL-17/IL-23 axis of inflammation in cancer: friend or foe? Curr Opin Investig Drugs 2009; 10: 543-549.
80. Murugaiyan G, Saha B. Protumor vs antitumor functions of IL-17. J Immunol 2009; 183: 4169-4175.
81. Dinarello CA. Interleukin-1 and interleukin-1 antagonism. Blood 1991; 77: 1627-1652.
82. Dinarello CA. Biologic basis for interleukin-1 in disease. Blood 1996; 87: 2095-2147.
83. Chen Z, Malhotra PS, Thomas GR, Ondrey FG, Duffey DC, Smith CW et al. Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer. Clin Cancer Res 1999; 5: 1369-1379.
84. Lewis AM, Varghese S, Xu H, Alexander HR. Interleukin-1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment. J Transl Med 2006; 4: 48.
85. Voronov E, Shouval DS, Krelin Y, Cagnano E, Benharroch D, Iwakura Y et al. IL-1 is required for tumor invasiveness and angiogenesis. Proc Natl Acad Sci USA 2003; 100: 2645-2650.
86. Portier M, Zhang XG, Ursule E, Lees D, Jourdan M, Bataille R et al. Cytokine gene expression in human multiple myeloma. Br J Haematol 1993; 85: 514-520.
87. Mitsunaga S, Ikeda M, Shimizu S, Ohno I, Furuse J, Inagaki M et al. Serum levels of IL-6 and IL-1beta can predict the efficacy of gemcitabine in patients with advanced pancreatic cancer. Br J Cancer 2013; 108: 2063-2069.
88. Lust JA, Lacy MQ, Zeldenrust SR, Dispenzieri A, Gertz MA, Witzig TE et al. Induction of a chronic disease state in patients with smoldering or indolent multiple myeloma by targeting interleukin 1{beta}-induced interleukin 6 production and the myeloma proliferative component. Mayo Clin Proc 2009; 84: 114-122.
89. Schindler C, Shuai K, Prezioso VR, Darnell Jr JE. Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Science 1992; 257: 809-813.
90. Akira S, Nishio Y, Inoue M, Wang XJ, Wei S, Matsusaka T et al. Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway. Cell 1994; 77: 63-71.
91. Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C et al. Stat3 as an oncogene. Cell 1999; 98: 295-303.
92. Bar-Natan M, Nelson EA, Xiang M, Frank DA. STAT signaling in the pathogenesis and treatment of myeloid malignancies. JAKSTAT 2012; 1: 55-64.
93. Frank DA. STAT3 as a central mediator of neoplastic cellular transformation. Cancer Lett 2007; 251: 199-210.
94. Fagard R, Metelev V, Souissi I, Baran-Marszak F. STAT3 inhibitors for cancer therapy: Have all roads been explored? JAKSTAT 2013; 2: e22882.
95. Yu CL, Meyer DJ, Campbell GS, Larner AC, Carter-Su C, Schwartz J et al. Enhanced DNA-binding activity of a Stat3-related protein in cells transformed by the Src oncoprotein. Science 1995; 269: 81-83.
96. Chiarle R, Simmons WJ, Cai H, Dhall G, Zamo A, Raz R et al. Stat3 is required for ALK-mediated lymphomagenesis and provides a possible therapeutic target. Nat Med 2005; 11: 623-629.
97. Gough DJ, Corlett A, Schlessinger K, Wegrzyn J, Larner AC, Levy DE. Mitochondrial STAT3 supports Ras-dependent oncogenic transformation. Science 2009; 324: 1713-1716.
98. Schlessinger K, Levy DE. Malignant transformation but not normal cell growth depends on signal transducer and activator of transcription 3. Cancer Res 2005; 65: 5828-5834.
99. Kortylewski M, Xin H, Kujawski M, Lee H, Liu Y, Harris T et al. Regulation of the IL-23 and IL-12 balance by Stat3 signaling in the tumor microenvironment. Cancer Cell 2009; 15: 114-123.
100. Gu FM, Li QL, Gao Q, Jiang JH, Huang XY, Pan JF et al. Sorafenib inhibits growth and metastasis of hepatocellular carcinoma by blocking STAT3. World J Gastroenterol 2011; 17: 3922-3932.
101. Horiguchi A, Asano T, Kuroda K, Sato A, Asakuma J, Ito K et al. STAT3 inhibitor WP1066 as a novel therapeutic agent for renal cell carcinoma. Br J Cancer 2010; 102: 1592-1599.
102. Huang C, Yang G, Jiang T, Cao J, Huang KJ, Qiu ZJ. Down-regulation of STAT3 expression by vector-based small interfering RNA inhibits pancreatic cancer growth. World J Gastroenterol 2011; 17: 2992-3001.
103. Sen M, Thomas SM, Kim S, Yeh JI, Ferris RL, Johnson JT et al. First-in-human trial of a STAT3 decoy oligonucleotide in head and neck tumors: implications for cancer therapy. Cancer Discov 2012; 2: 694-705.
104. Abdulghani J, Gu L, Dagvadorj A, Lutz J, Leiby B, Bonuccelli G et al. Stat3 promotes metastatic progression of prostate cancer. Am J Pathol 2008; 172: 1717-1728.
105. Fukuda A, Wang SC, JPt Morris, Folias AE, Liou A, Kim GE et al. Stat3 and MMP7 contribute to pancreatic ductal adenocarcinoma initiation and progression. Cancer Cell 2011; 19: 441-455.
106. Kryczek I, Lin Y, Nagarsheth N, Peng D, Zhao L, Zhao E et al. IL-22(+)CD4(+) T cells promote colorectal cancer stemness via STAT3 transcription factor activation and induction of the methyltransferase DOT1L. Immunity 2014; 40: 772-784.
107. Keir ME, Liang SC, Guleria I, Latchman YE, Qipo A, Albacker LA et al. Tissue expression of PD-L1 mediates peripheral T cell tolerance. J Exp Med 2006; 203: 883-895.
108. Okazaki T, Honjo T. The PD-L pathway in immunological tolerance. Trends Immunol 2006; 27: 195-201.
109. Ghebeh H, Mohammed S, Al-Omair A, Qattan A, Lehe C, Al-Qudaihi G et al. The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors. Neoplasia 2006; 8: 190-198.
110. Harvey RD. Immunologic and clinical effects of targeting PD-1 in lung cancer. Clin Pharmacol Ther 2014; 96: 214-223.
111. Hino R, Kabashima K, Kato Y, Yagi H, Nakamura M, Honjo T et al. Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma. Cancer 2010; 116: 1757-1766.
112. Nomi T, Sho M, Akahori T, Hamada K, Kubo A, Kanehiro H et al. Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer. Clin Cancer Res 2007; 13: 2151-2157.
113. Wilcox RA, Ansell SM, Lim MS, Zou W, Chen L. The B7 homologues and their receptors in hematologic malignancies. Eur J Haematol 2012; 88: 465-475.
114. Hamanishi J, Mandai M, Iwasaki M, Okazaki T, Tanaka Y, Yamaguchi K et al. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci USA 2007; 104: 3360-3365.
115. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA 2002; 99: 12293-12297.
116. Iwai Y, Terawaki S, Honjo T. PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells. Int Immunol 2005; 17: 133-144.
117. Okudaira K, Hokari R, Tsuzuki Y, Okada Y, Komoto S, Watanabe C et al. Blockade of B7-H1 or B7-DC induces an anti-tumor effect in a mouse pancreatic cancer model. Int J Oncol 2009; 35: 741-749.
118. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Eng J Med 2012; 366: 2455-2465.
119. Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH 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: 3167-3175.
120. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Eng J Med 2012; 366: 2443-2454.
121. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012; 12: 252-264.
122. Blank CU, Enk A. Therapeutic use of anti-CTLA-4 antibodies. Int Immunol 2014; 27: 3-10.
123. Walker LS, Sansom DM. The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses. Nat Rev Immunol 2011; 11: 852-863.
124. Pentcheva-Hoang T, Simpson TR, Montalvo-Ortiz W, Allison JP. Cytotoxic T lymphocyte antigen-4 blockade enhances antitumor immunity by stimulating melanoma-specific T-cell motility. Cancer Immunol Res 2014; 2: 970-980.
125. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Eng J Med 2010; 363: 711-723.
126. Ribas A, Kefford R, Marshall MA, Punt CJ, Haanen JB, Marmol M et al. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J Clin Oncol 2013; 31: 616-622.
127. Tait Wojno ED, Artis D. Innate lymphoid cells: balancing immunity, inflammation, and tissue repair in the intestine. Cell Host Microbe 2012; 12: 445-457.
128. Spits H, Cupedo T. Innate lymphoid cells: emerging insights in development, lineage relationships, and function. Annu Rev Immunol 2012; 30: 647-675.
129. Kirchberger S, Royston DJ, Boulard O, Thornton E, Franchini F, Szabady RL et al. Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model. J Exp Med 2013; 210: 917-931.
130. Shields JD, Kourtis IC, Tomei AA, Roberts JM, Swartz MA. Induction of lymphoidlike stroma and immune escape by tumors that express the chemokine CCL21. Science 2010; 328: 749-752.
131. Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 2009; 9: 162-174.
132. Greten TF, Manns MP, Korangy F. Myeloid derived suppressor cells in human diseases. Int Immunopharmacol 2011; 11: 802-807.
133. Markowitz J, Wesolowski R, Papenfuss T, Brooks TR, Carson WE 3rd. Myeloidderived suppressor cells in breast cancer. Breast Cancer Res Treat 2013; 140: 13-21.
134. Sinha P, Clements VK, Bunt SK, Albelda SM, Ostrand-Rosenberg S. Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol 2007; 179: 977-983.
135. Kusmartsev S, Nefedova Y, Yoder D, Gabrilovich DI. Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J Immunol 2004; 172: 989-999.
136. Ochoa AC, Zea AH, Hernandez C, Rodriguez PC. Arginase, prostaglandins, and myeloid-derived suppressor cells in renal cell carcinoma. Clin Cancer Res 2007; 13: 721s-726s.
137. Filipazzi P, Huber V, Rivoltini L. Phenotype, function and clinical implications of myeloid-derived suppressor cells in cancer patients. Cancer Immunol Immunother 2012; 61: 255-263.
138. Movahedi K, Guilliams M, Van den Bossche J, Van den Bergh R, Gysemans C, Beschin A et al. Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity. Blood 2008; 111: 4233-4244.
139. Mundy-Bosse BL, Young GS, Bauer T, Binkley E, Bloomston M, Bill MA et al. Distinct myeloid suppressor cell subsets correlate with plasma IL-6 and IL-10 and reduced interferon-alpha signaling in CD4(+) T cells from patients with GI malignancy. Cancer Immunol Immunother 2011; 60: 1269-1279.
140. Najjar YG, Finke JH. Clinical perspectives on targeting of myeloid derived suppressor cells in the treatment of cancer. Front Oncol 2013; 3: 49.
141. Fujimoto S, Greene M, Sehon AH. Immunosuppressor T cells in tumor bearing host. Immunol Commun 1975; 4: 201-217.
142. Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nature reviews Immunology 2006; 6: 295-307.
143. Darrasse-Jeze G, Podsypanina K. How numbers, nature, and immune status of foxp3 regulatory T-cells shape the early immunological events in tumor development. Front Immunol 2013; 4: 292.
144. Bates GJ, Fox SB, Han C, Leek RD, Garcia JF, Harris AL et al. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol 2006; 24: 5373-5380.
145. Ladoire S, Arnould L, Apetoh L, Coudert B, Martin F, Chauffert B et al. Pathologic complete response to neoadjuvant chemotherapy of breast carcinoma is associated with the disappearance of tumor-infiltrating foxp3+ regulatory T cells. Clin Cancer Res 2008; 14: 2413-2420.
146. Greten TF, Ormandy LA, Fikuart A, Hochst B, Henschen S, Horning M et al. Lowdose cyclophosphamide treatment impairs regulatory T cells and unmasks AFPspecific CD4+ T-cell responses in patients with advanced HCC. J Immunother 2010; 33: 211-218.
147. Onizuka S, Tawara I, Shimizu J, Sakaguchi S, Fujita T, Nakayama E. Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res 1999; 59: 3128-3133.
148. Shimizu J, Yamazaki S, Sakaguchi S. Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity. J Immunol 1999; 163: 5211-5218.
149. Mantovani A, Bottazzi B, Colotta F, Sozzani S, Ruco L. The origin and function of tumor-associated macrophages. Immunol Today 1992; 13: 265-270.
150. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 2004; 25: 677-686.
151. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986; 136: 2348-2357.
152. Watkins SK, Egilmez NK, Suttles J, Stout RD. IL-12 rapidly alters the functional profile of tumor-associated and tumor-infiltrating macrophages in vitro and in vivo. J Immunol 2007; 178: 1357-1362.
153. Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol 2008; 8: 958-969.
154. Nakanishi Y, Nakatsuji M, Seno H, Ishizu S, Akitake-Kawano R, Kanda K et al. COX-2 inhibition alters the phenotype of tumor-associated macrophages from M2 to M1 in ApcMin/+ mouse polyps. Carcinogenesis 2011; 32: 1333-1339.
155. Arber N, Eagle CJ, Spicak J, Racz I, Dite P, Hajer J et al. Celecoxib for the prevention of colorectal adenomatous polyps. N Eng J Med 2006; 355: 885-895.
156. Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science 2011; 331: 1612-1616.
157. Huang B, Lei Z, Zhang GM, Li D, Song C, Li B et al. SCF-mediated mast cell infiltration and activation exacerbate the inflammation and immunosuppression in tumor microenvironment. Blood 2008; 112: 1269-1279.
158. Yang Z, Zhang B, Li D, Lv M, Huang C, Shen GX et al. Mast cells mobilize myeloidderived suppressor cells and Treg cells in tumor microenvironment via IL-17 pathway in murine hepatocarcinoma model. PLoS One 2010; 5: e8922.
159. Johansson A, Rudolfsson S, Hammarsten P, Halin S, Pietras K, Jones J et al. Mast cells are novel independent prognostic markers in prostate cancer and represent a target for therapy. Am J Pathol 2010; 177: 1031-1041.
160. Rabenhorst A, Schlaak M, Heukamp LC, Forster A, Theurich S, von Bergwelt-Baildon M et al. Mast cells play a protumorigenic role in primary cutaneous lymphoma. Blood 2012; 120: 2042-2054.
161. Wasiuk A, Dalton DK, Schpero WL, Stan RV, Conejo-Garcia JR, Noelle RJ. Mast cells impair the development of protective anti-tumor immunity. Cancer Immunol Immunother 2012; 61: 2273-2282.
162. Kim YJ, Hong KS, Chung JW, Kim JH, Hahm KB. Prevention of colitis-associated carcinogenesis with infliximab. Cancer Prev Res (Phila) 2010; 3: 1314-1333.
163. Melillo RM, Guarino V, Avilla E, Galdiero MR, Liotti F, Prevete N et al. Mast cells have a protumorigenic role in human thyroid cancer. Oncogene 2010; 29: 6203-6215.
164. Oka T, Kalesnikoff J, Starkl P, Tsai M, Galli SJ. Evidence questioning cromolyn's effectiveness and selectivity as a 'mast cell stabilizer' in mice. Lab Invest 2012; 92: 1472-1482.
165. Gresser I. Biologic effects of interferons. J Invest Dermatol 1990; 95: 66S-71S.
166. Nanus DM, Pfeffer LM, Bander NH, Bahri S, Albino AP. Antiproliferative and antitumor effects of alpha-interferon in renal cell carcinomas: correlation with the expression of a kidney-associated differentiation glycoprotein. Cancer Res 1990; 50: 4190-4194.
167. Rizza P, Moretti F, Belardelli F. Recent advances on the immunomodulatory effects of IFN-alpha: implications for cancer immunotherapy and autoimmunity. Autoimmunity 2010; 43: 204-209.
168. Theofilopoulos AN, Baccala R, Beutler B, Kono DH. Type I interferons (alpha/beta) in immunity and autoimmunity. Annu Rev Immunol 2005; 23: 307-336.
169. Jego G, Palucka AK, Blanck JP, Chalouni C, Pascual V, Banchereau J. Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. Immunity 2003; 19: 225-234.
170. Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol 1996; 14: 7-17.
171. Sun M, Lughezzani G, Perrotte P, Karakiewicz PI. Treatment of metastatic renal cell carcinoma. Nat Rev Urol 2010; 7: 327-338.
172. Kilinc MO, Gu T, Harden JL, Virtuoso LP, Egilmez NK. Central role of tumorassociated CD8+ T effector/memory cells in restoring systemic antitumor immunity. J Immunol 2009; 182: 4217-4225.
173. Cuff S, Dolton G, Matthews RJ, Gallimore A. Antigen specificity determines the pro-or antitumoral nature of CD8+ T cells. J Immunol 2010; 184: 607-614.
174. Mahmoud SM, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AH et al. Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol 2011; 29: 1949-1955.
175. Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 2000; 100: 655-669.
176. Thierfelder WE, van Deursen JM, Yamamoto K, Tripp RA, Sarawar SR, Carson RT et al. Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells. Nature 1996; 382: 171-174.
177. Lazarevic V, Glimcher LH, Lord GM. T-bet: a bridge between innate and adaptive immunity. Nat Rev Immunol 2013; 13: 777-789.
178. Hung K, Hayashi R, Lafond-Walker A, Lowenstein C, Pardoll D, Levitsky H. The central role of CD4(+) T cells in the antitumor immune response. J Exp Med 1998; 188: 2357-2368.
179. Sharma RK, Yolcu ES, Srivastava AK, Shirwan H. CD4+ T cells play a critical role in the generation of primary and memory antitumor immune responses elicited by SA-4-1BBL and TAA-based vaccines in mouse tumor models. PLoS One 2013; 8: e73145.
180. Gu-Trantien C, Loi S, Garaud S, Equeter C, Libin M, de Wind A et al. CD4(+) follicular helper T cell infiltration predicts breast cancer survival. J Clin Invest 2013; 123: 2873-2892.
181. Linnemann C, van Buuren MM, Bies L, Verdegaal EM, Schotte R, Calis JJ et al. High-throughput epitope discovery reveals frequent recognition of neoantigens by CD4+ T cells in human melanoma. Nat Med 2015; 21: 81-85.
182. Kronenberg M. Toward an understanding of NKT cell biology: progress and paradoxes. Annu Rev Immunol 2005; 23: 877-900.
183. Molling JW, Langius JA, Langendijk JA, Leemans CR, Bontkes HJ, van der Vliet HJ et al. Low levels of circulating invariant natural killer T cells predict poor clinical outcome in patients with head and neck squamous cell carcinoma. J Clin Oncol 2007; 25: 862-868.
184. Tachibana T, Onodera H, Tsuruyama T, Mori A, Nagayama S, Hiai H et al. Increased intratumor Valpha24-positive natural killer T cells: a prognostic factor for primary colorectal carcinomas. Clin Cancer Res 2005; 11: 7322-7327.
185. Fuji N, Ueda Y, Fujiwara H, Toh T, Yoshimura T, Yamagishi H. Antitumor effect of alpha-galactosylceramide (KRN7000) on spontaneous hepatic metastases requires endogenous interleukin 12 in the liver. Clin Cancer Res 2000; 6: 3380-3387.
186. Giaccone G, Punt CJ, Ando Y, Ruijter R, Nishi N, Peters M et al. A phase I study of the natural killer T-cell ligand alpha-galactosylceramide (KRN7000) in patients with solid tumors. Clin Cancer Res 2002; 8: 3702-3709.
187. Chang YJ, Huang JR, Tsai YC, Hung JT, Wu D, Fujio M et al. Potent immunemodulating and anticancer effects of NKT cell stimulatory glycolipids. Proc Natl Acad Sci USA 2007; 104: 10299-10304.
188. Vicari AP, Caux C, Trinchieri G. Tumour escape from immune surveillance through dendritic cell inactivation. Semin Cancer Biol 2002; 12: 33-42.
189. Hegmans JP, Aerts JG. Immunomodulation in cancer. Curr Opin Pharmacol 2014; 17C: 17-21.
190. Zeid NA, Muller HK. S100 positive dendritic cells in human lung tumors associated with cell differentiation and enhanced survival. Pathology 1993; 25: 338-343.