The role of IL-27 in the induction of anti-tumor cytotoxic T lymphocyte response

American Journal of Translational Research

Volumn 5, Issue 5, 2013, Pages 470-480

  Liu, Zhenzhen ^a   Yu, Jianhua ^a   Carson III, William E ^a   Bai, Xue Feng ^a  

^a OHIO STATE UNIVERSITY   (United States)

Author keywords

Anti tumor cytotoxic T lymphocyte (CTLs); Cancer; IL 21; IL 27; p28; p35; p53

Indexed keywords

CASPASE 3; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; GAMMA INTERFERON; GLYCOPROTEIN GP 130; GRANZYME B; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 21; INTERLEUKIN 27; JANUS KINASE 1; PROTEIN BCL 2; PROTEIN BCL 6; PROTEIN P28; PROTEIN TYROSINE KINASE; STAT PROTEIN; STAT3 PROTEIN; TRANSCRIPTION FACTOR FOXP3; TUMOR ANTIGEN; VIMENTIN;

ANGIOGENESIS; ANTINEOPLASTIC ACTIVITY; ARTICLE; CD8+ T LYMPHOCYTE; CELL DEATH; CELL DIFFERENTIATION; CELL PROLIFERATION; CYTOTOXIC T LYMPHOCYTE; HUMAN; IMMUNE RESPONSE; LUNG CANCER; MEMORY T LYMPHOCYTE; NEOPLASM; NONHUMAN; PHENOTYPE; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; TUMOR IMMUNITY; TUMOR MICROENVIRONMENT; UPREGULATION;

HUMAN HERPESVIRUS 4;

EID: 84882941082     PISSN: None     EISSN: 19438141     Source Type: Journal    
DOI: None     Document Type: Article

References (94)

1. Giovarelli M, Musiani P, Modesti A, Dellabona P, Casorati G, Allione A, Consalvo M, Cavallo F, di Pierro F, De Giovanni C, et al. Local release of IL-10 by transfected mouse mammary adenocarcinoma cells does not suppress but enhances antitumor reaction and elicits a strong cytotoxic lymphocyte and antibody-dependent immune memory. J Immunol 1995; 155: 3112-3123.
2. Berman RM, Suzuki T, Tahara H, Robbins PD, Narula SK and Lotze MT. Systemic administration of cellular IL-10 induces an effective, spe cific, and long-lived immune response against established tumors in mice. J Immunol 1996; 157: 231-238.
3. Mumm JB, Emmerich J, Zhang X, Chan I, Wu L, Mauze S, Blaisdell S, Basham B, Dai J, Grein J, Sheppard C, Hong K, Cutler C, Turner S, Laface D, Kleinschek M, Judo M, Ayanoglu G, Langowski J, Gu D, Paporello B, Murphy E, Sriram V, Naravula S, Desai B, Medicherla S, Seghezzi W, McClanahan T, Cannon-Carlson S, Beebe AM and Oft M. IL-10 Elicits IFNgammaDependent Tumor Immune Surveillance. Cancer Cell 2011; 20: 781-796.
4. Ma HL, Whitters MJ, Konz RF, Senices M, Young DA, Grusby MJ, Collins M and DunussiJoannopoulos K. IL-21 activates both innate and adaptive immunity to generate potent antitumor responses that require perforin but are independent of IFN-gamma. J Immunol 2003; 171: 608-615.
5. Kishida T, Asada H, Itokawa Y, Cui FD, Shin-Ya M, Gojo S, Yasutomi K, Ueda Y, Yamagishi H, Imanishi J and Mazda O. Interleukin (IL)-21 and IL-15 genetic transfer synergistically augments therapeutic antitumor immunity and promotes regression of metastaticlymphoma. Mol Ther 2003; 8: 552-558.
6. Di Carlo E, Comes A, Orengo AM, Rosso O, Meazza R, Musiani P, Colombo MP and Ferrini S. IL-21 induces tumor rejection by specific CTL and IFN-gamma-dependent CXC chemokines in syngeneic mice. J Immunol 2004; 172: 1540-1547.
7. Smyth MJ, Hayakawa Y, Cretney E Zerafa N,Sivakumar P, Yagita H and Takeda K., IL-21 enhances tumor-specific CTL induction by antiDR5 antibody therapy. J Immunol 2006; 176: 6347-6355.
8. Salcedo R, Stauffer JK, Lincoln E, Back TC, Hixon JA, Hahn C, Shafer-Weaver K, Malyguine A, Kastelein R and Wigginton JM. IL-27 mediates complete regression of orthotopic primary and metastatic murine neuroblastoma tumors: role for CD8+ T cells. J Immunol 2004; 173: 7170-7182.
9. Hisada M, Kamiya S, Fujita K, Belladonna ML, Aoki T, Koyanagi Y, Mizuguchi J and Yoshimoto T. Potent antitumor activity of interleukin-27. Cancer Res 2004; 64: 1152-1156.
10. Chiyo M, Shimozato O, Iizasa T, Fujisawa T and Tagawa M. Antitumor effects produced by transduction of dendritic cells-derived heterodimeric cytokine genes in murine colon carcinoma cells. Anticancer Res 2004; 24: 3763-3767.
11. Chiyo M, Shimozato O, Yu L, Kawamura K, Iizasa T, Fujisawa T and Tagawa M. Expression of IL-27 in murine carcinoma cells produces antitumor effects and induces protective im munity in inoculated host animals. Int J Cancer 2005; 115: 437-442.
12. Salcedo R, Hixon JA, Stauffer JK, Jalah R, Brooks AD, Khan T, Dai RM, Scheetz L, Lincoln E, Back TC, Powell D, Hurwitz AA, Sayers TJ, Kastelein R, Pavlakis GN, Felber BK, Trinchieri G and Wigginton JM. Immunologic and therapeutic synergy of IL-27 and IL-2: enhancement of T cell sensitization, tumor-specific CTL reactivity and complete regression of disseminated neuroblastoma metastases in the liver and bone marrow. J Immunol 2009; 182: 4328-4338.
13. Colombo MP and Trinchieri G. Interleukin-12 in anti-tumor immunity and immunotherapy. Cytokine Growth Factor Rev 2002; 13: 155-168.
14. Del Vecchio M, Bajetta E, Canova S, Lotze MT, Wesa A, Parmiani G and Anichini A. Interleukin-12: biological properties and clinical application. Clin Cancer Res 2007; 13: 4677-4685.
15. Rosenberg SA, Yang JC and Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat Med 2004; 10: 909-915.
16. Yang ZZ, Grote DM, Ziesmer SC, Niki T, Hirashima M, Novak AJ, Witzig TE and Ansell SM. IL-12 upregulates TIM-3 expression and induces T cell exhaustion in patients with follicular B cell non-Hodgkin lymphoma. J Clin Invest 2012; 122: 1271-1282.
17. Zhu S, Lee DA and Li S. IL-12 and IL-27 sequential gene therapy via intramuscular electroporation delivery for eliminating distal aggressive tumors. J Immunol 2010; 184: 2348-2354.
18. Shinozaki Y, Wang S, Miyazaki Y, Miyazaki K, Yamada H, Yoshikai Y, Hara H and Yoshida H. Tumor-specific cytotoxic T cell generation and dendritic cell function are differentially regulated by interleukin 27 during development of anti-tumor immunity. Int J Cancer 2009; 124: 1372-1378.
19. Morishima N, Mizoguchi I, Okumura M, Chiba Y, Xu M, Shimizu M, Matsui M, Mizuguchi J and Yoshimoto T. A pivotal role for interleukin-27 in CD8+ T cell functions and generation of cytotoxic T lymphocytes. J Biomed Biotechnol 2010; 2010: 6054-6083.
20. Natividad KD, Junankar SR, Mohd Redzwan N, Nair R, Wirasinha RC, King C, Brink R, Swarbrick A and Batten M. Interleukin-27 Signaling Promotes Immunity against Endogenously Arising Murine Tumors. PLoS One 2013; 8: e57469.
21. Pflanz S, Timans JC, Cheung J, Rosales R, Kanzler H, Gilbert J, Hibbert L, Churakova T, Travis M, Vaisberg E, Blumenschein WM, Mattson JD, Wagner JL, To W, Zurawski S, McClanahan TK, Gorman DM, Bazan JF de Waal Malefyt R, Rennick D and Kastelein RA., IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4(+) T cells. Immunity 2002; 16: 779-790.
22. Larousserie F, Pflanz S, Coulomb-L'Hermine A, Brousse N, Kastelein R and Devergne O. Expression of IL-27 in human Th1-associated granulomatous diseases. J Pathol 2004; 202: 164-171.
23. Sonobe Y, Yawata I, Kawanokuchi J, Takeuchi H, Mizuno T and Suzumura A. Production of IL27 and other IL-12 family cytokines by microglia and their subpopulations. Brain Res 2005; 1040: 202-207.
24. Pflanz S, Hibbert L, Mattson JRosales R,Vaisberg E, Bazan JF, Phillips JH, McClanahan TK, de Waal Malefyt R and Kastelein RA., WSX1 and glycoprotein 130 constitute a signaltransducing receptor for IL-27. J Immunol 2004; 172: 2225-2231.
25. Batten M and Ghilardi N. The biology and therapeutic potential of interleukin 27. J Mol Med (Berl) 2007; 85: 661-672.
26. Scheller J, Schuster B, Holscher C, Yoshimoto T and Rose-John S. No inhibition of IL-27 signaling by soluble gp130. Biochem Biophys Res Commun 2005; 326: 724-728.
27. Lucas S, Ghilardi N, Li Jand de Sauvage FJ.IL27 regulates IL-12 responsiveness of naive CD4+ T cells through Stat1-dependent and -independent mechanisms. Proc Natl Acad Sci U S ssssss 15047-15052.
28. Takeda A, Hamano S, Yamanaka A Hanada T,Ishibashi T, Mak TW, Yoshimura A and Yoshida H., Cutting edge: role of IL-27/WSX-1 signaling for induction of T-bet through activation of STAT1 during initial Th1 commitment. J Immunol 2003; 170: 4886-4890.
29. Hanada T, Ishibashi T, Mak TW, Yoshimura A and Yoshida H, Mizuguchi J and Yoshimoto T. An indispensable role for STAT1 in IL-27-induced T-bet expression but not proliferation of naive CD4+ T cells. J Immunol 2004; 173: 3871-3877.
30. Yoshimura T, Takeda A, Hamano S, Miyazaki Y, Kinjyo I, Ishibashi T, Yoshimura A and Yoshida H. Two-sided roles of IL-27: induction of Th1 differentiation on naive CD4+ T cells versus suppression of proinflammatory cytokine production including IL-23-induced IL-17 on activated CD4+ T cells partially through STAT3dependent mechanism. J Immunol 2006; 177: 5377-5385.
31. Schindler C, Shuai K, Prezioso VR and Darnell JE Jr. Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Science 1992; 257: 809-813.
32. Shuai K, Schindler C, Prezioso VR and Darnell JE Jr. Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein. Science 1992; 258: 1808-1812.
33. Stahl N, Boulton TG, Farruggella T, Ip NY, Davis S, Witthuhn BA, Quelle FW, Silvennoinen O, Barbieri G, Pellegrini S, et al. Association and activation of Jak-Tyk kinases by CNTF-LIF-OSMIL-6 beta receptor components. Science 1994; 263: 92-95.
34. Heinrich PC, Horn F, Graeve L, Dittrich E, Kerr I, Muller-Newen G, Grotzinger J and Wollmer A. Interleukin-6 and related cytokines: effect on the acute phase reaction. Z Ernahrungswiss 1998; 37 Suppl 1: 43-49.
35. Hall AO, Silver JS and Hunter CA. The immunobiology of IL-27. Adv Immunol 2012; 115: 1-44.
36. Chen Q, Ghilardi N, Wang H, Baker T, Xie MH, Gurney A, Grewal IS and de Sauvage FJ. Development of Th1-type immune responses requires the type I cytokine receptor TCCR. Nature 2000; 407: 916-920.
37. Hamano S, Himeno K, Miyazaki Y, Ishii K, Yamanaka A, Takeda A, Zhang M, Hisaeda H, Mak TW, Yoshimura A and Yoshida H. WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production. Immunity 2003; 19: 657-667.
38. Holscher C, Holscher A, Ruckerl D, Yoshimoto T, Yoshida H, Mak T, Saris C and Ehlers S. The IL-27 receptor chain WSX-1 differentially regulates antibacterial immunity and survival during experimental tuberculosis. J Immunol 2005; 174: 3534-3544.
39. Diveu C, McGeachy MJ, Boniface K, Stumhofer JS, Sathe M, Joyce-Shaikh B, Chen Y, Tato CM, McClanahan TK, de Waal Malefyt R, Hunter CA, Cua DJ and Kastelein R. IL-27 blocks RORc expression to inhibit lineage commitment of Th17 cells. J Immunol 2009; 182: 5748-5756.
40. Neufert C, Becker C, Wirtz S, Fantini MC, Weigmann B, Galle PR and Neurath MF. IL-27 controls the development of inducible regulatory T cells and Th17 cells via differential effects on STAT1. Eur J Immunol 2007; 37: 18091816.
41. Huber M, Steinwald V, Guralnik A, Brustle A, Kleemann P, Rosenplanter C, Decker T and Lohoff M. IL-27 inhibits the development of regulatory T cells via STAT3. Int Immunol 2008; 20: 223-234.
42. Stumhofer JS, Silver JS, Laurence A, Porrett PM, Harris TH, Turka LA, Ernst M, Saris CJ, O'Shea JJ and Hunter CA. Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nat Immunol 2007; 8: 13631371.
43. Awasthi A, Carrier Y, Peron JP, Bettelli E, Kamanaka M, Flavell RA, Kuchroo VK, Oukka M and Weiner HL. A dominant function for in terleukin 27 in generating interleukin 10-producing anti-inflammatory T cells. Nat Immunol 2007; 8: 1380-1389.
44. Fitzgerald DC, Ciric B, Touil T, Harle H, Grammatikopolou J, Das Sarma J, Gran B, Zhang GX and Rostami A. Suppressive effect of IL-27 on encephalitogenic Th17 cells and the effector phase of experimental autoimmune encephalomyelitis. J Immunol 2007; 179: 3268-3275.
45. [Batten M, Kljavin NM, Li J, Walter MJ, de Sauvage FJ and Ghilardi N. Cutting edge: IL-27 is a potent inducer of IL-10 but not FoxP3 in murine T cells. J Immunol 2008; 180: 2752-2756.
46. Hunter CA and Kastelein R. Interleukin-27: balancing protective and pathological immunity. Immunity 2012; 37: 960-969.
47. Pot C, Jin H, Awasthi A, Liu SM, Lai CY, Madan R, Sharpe AH, Karp CL, Miaw SC, Ho IC and Kuchroo VK. Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells. J Immunol 2009; 183: 797-801.
48. Xu J, Yang Y, Qiu G, Lal G, Wu Z, Levy DE, Ochando JC Bromberg JS and Ding Y., c-Maf regulates IL-10 expression during Th17 polarization. J Immunol 2009; 182: 6226-6236.
49. Apetoh L, Quintana FJ, Pot C, Joller N, Xiao S, Kumar D, Burns EJ, Sherr DH, Weiner HL and Kuchroo VK. The aryl hydrocarbon receptor interacts with c-Maf to promote the differentiation of type 1 regulatory T cells induced by IL27. Nat Immunol 2010; 11: 854-861.
50. Batten M, Ramamoorthi N, Kljavin NM, Ma CS, Cox JH, Dengler HS, Danilenko DM, Caplazi P, Wong M, Fulcher DA, Cook MC, King C, Tangye SG, de Sauvage FJ and Ghilardi N. IL-27 supports germinal center function by enhancing IL-21 production and the function of T follicular helper cells. J Exp Med 2010; 207: 28952906.
51. Wei L, Laurence A, Elias KM and O'Shea JJ. IL21 is produced by Th17 cells and drives IL-17 production in a STAT3-dependent manner. J Biol Chem 2007; 282: 34605-34610.
52. Takemoto N, Intlekofer AM, Northrup JT, Wherry EJ and Reiner SL.: Cutting Edge IL-12 inversely regulates T-bet and eomesodermin expression during pathogen-induced CD8+ T cell differentiation. J Immunol 2006; 177: 7515-7519.
53. Kerkar SP, Goldszmid RS, Muranski P, Chinnasamy D, Yu Z, Reger RN, Leonardi AJ, Morgan RA, Wang E, Marincola FM, Trinchieri G, Rosenberg SA and Restifo NP. IL-12 triggers a programmatic change in dysfunctional my eloid-derived cells within mouse tumors. J Clin Invest 2011; 121: 4746-4757.
54. Murugaiyan G and Saha B. IL-27 in tumor immunity and immunotherapy. Trends Mol Med 2013; 19: 108-116.
55. Oniki S, Nagai H, Horikawa T, Furukawa J, Belladonna ML, Yoshimoto T, Hara I and Nishigori C. Interleukin-23 and interleukin-27 exert quite different antitumor and vaccine effects on poorly immunogenic melanoma. Cancer Res 2006; 66: 6395-6404.
56. Shimizu M, Shimamura M, Owaki T, Asakawa M, Fujita K, Kudo M, Iwakura Y, Takeda Y, Luster AD, Mizuguchi J and Yoshimoto T. Antiangiogenic and antitumor activities of IL27. J Immunol 2006; 176: 7317-7324.
57. Yoshimoto T, Morishima N, Mizoguchi I, Shimizu M, Nagai H, Oniki S, Oka M, Nishigori C and Mizuguchi J. Antiproliferative activity of IL-27 on melanoma. J Immunol 2008; 180: 6527-6535.
58. Matsui M, Kishida T, Nakano H, Yoshimoto K, Shin-Ya M, Shimada T, Nakai S, Imanishi J, Yoshimoto T, Hisa Y and Mazda O. Interleukin-27 activates natural killer cells and suppresses NK-resistant head and neck squamous cell carcinoma through inducing antibody-dependent cellular cytotoxicity. Cancer Res 2009; 69: 2523-2530.
59. Ho MY, Leu SJ, Sun GH, Tao MH, Tang SJ and Sun KH. IL-27 directly restrains lung tumorigenicity by suppressing cyclooxygenase-2-mediatedactivities. J Immunol 2009; 183: 6217-6226.
60. Cocco C, Giuliani N, Di Carlo E, Ognio EStorti P, Abeltino M, Sorrentino C, Ponzoni M, Ribatti D and Airoldi I., Interleukin-27 acts as multifunctional antitumor agent in multiple myeloma. Clin Cancer Res 2010; 16: 4188-4197.
61. Schneider R, Yaneva T, Beauseigle D, ElKhoury L and Arbour N. IL-27 increases the proliferation and effector functions of human naive CD8+ T lymphocytes and promotes their development into Tc1 cells. Eur J Immunol 2011; 41: 47-59.
62. Morishima N, Owaki T, Asakawa M, Kamiya S, Mizuguchi J and Yoshimoto T. Augmentation of effector CD8+ T cell generation with enhanced granzyme B expression by IL-27. J Immunol 2005; 175: 1686-1693.
63. Mittal A, Murugaiyan G, Beynon V, Hu D and Weiner HL. IL-27 induction of IL-21 from human CD8+ T cells induces granzyme B in an autocrine manner. Immunol Cell Biol 2012; 90: 831-835.
64. Liu Z, Liu JQ, Talebian F, Wu LC, Li S and Bai XF. IL-27 enhances the survival of tumor antigenspecific CD8(+) T cells and programs them into IL-10-producing, memory precursor-like effector cells. Eur J Immunol 2013; 43: 468-479.
65. Liu JQ and Bai XF. Overcoming immune evasion in T cell therapy of cancer: lessons from animal models. Curr Mol Med 2008; 8: 68-75.
66. Kim G, Shinnakasu R, Saris CJ, Cheroutre H and Kronenberg M. A novel role for IL-27 in mediating the survival of activated mouse CD4 T lymphocytes. J Immunol 2013; 190: 15101518.
67. Cui W, Liu Y, Weinstein JS, Craft J and Kaech SM. An interleukin-21-interleukin-10-STAT3 pathway is critical for functional maturation of memory CD8+ T cells. Immunity 2011; 35: 792-805.
68. Zhang Y, Joe G, Hexner E, Zhu J and Emerson SG. Host-reactive CD8+ memory stem cells in graft-versus-host disease. Nat Med 2005; 11: 1299-1305.
69. Gattinoni L, Zhong XS, Palmer DC, Ji Y, Hinrichs CS, Yu Z, Wrzesinski C, Boni A, Cassard L, Garvin LM, Paulos CM, Muranski P and Restifo NP. Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells. Nat Med 2009; 15: 808-813.
70. Oestreich KJ, Huang AC and Weinmann AS. The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns. J Exp Med 2011; 208: 1001-1013.
71. Hirschhorn-Cymerman D, Budhu S, Kitano S, Liu C, Zhao F, Zhong H, Lesokhin AM, AvogadriConnors F, Yuan J, Li Y, Houghton AN, Merghoub T and Wolchok JD. Induction of tumoricidal function in CD4+ T cells is associated with concomitant memory and terminally differentiated phenotype. J Exp Med 2012; 209: 2113-2126.
72. Curran MA, Geiger TL, Montalvo W, Kim M, Reiner SL, Al-Shamkhani A, Sun JC and Allison JP. Systemic 4-1BB activation induces a novel T cell phenotype driven by high expression of Eomesodermin. J Exp Med 2013; 210: 743-755.
73. Tanikawa T, Wilke CM, Kryczek I, Chen GY, Kao J, Nunez G and Zou W. Interleukin-10 ablation promotes tumor development, growth, and metastasis. Cancer Res 2012; 72: 420-429.
74. Groux H, Cottrez F, Rouleau M, Mauze S, Antonenko S, Hurst S, McNeil T, Bigler M, Roncarolo MG and Coffman RL. A transgenic model to analyze the immunoregulatory role of IL-10 secreted by antigen-presenting cells. J Immunol 1999; 162: 1723-1729.
75. Noble A, Giorgini A and Leggat JA. Cytokineinduced IL-10-secreting CD8 T cells represent a phenotypically distinct suppressor T-cell lineage. Blood 2006; 107: 4475-4483.
76. Trandem K, Zhao J, Fleming E and Perlman S. Highly activated cytotoxic CD8 T cells express protective IL-10 at the peak of coronavirus-in duced encephalitis. J Immunol 2011; 186: 3642-3652.
77. Leonard WJ and Spolski R. Interleukin-21: a modulator of lymphoid proliferation, apoptosis and differentiation. Nat Rev Immunol 2005; 5: 688-698.
78. Spolski R and Leonard WJ. Interleukin-21: basic biology and implications for cancer and autoimmunity. Annu Rev Immunol 2008; 26: 5779.
79. Zeng R, Spolski R, Casas E, Zhu W, Levy DE and Leonard WJ. The molecular basis of IL-21mediated proliferation. Blood 2007; 109: 4135-4142.
80. Elsaesser H, Sauer K and Brooks DG. IL-21 is required to control chronic viral infection. Science 2009; 324: 1569-1572.
81. Yi JS, Du M and Zajac AJ. A vital role for interleukin-21 in the control of a chronic viral infection. Science 2009; 324: 1572-1576.
82. Yi JS, Ingram JT and Zajac AJ. IL-21 deficiency influences CD8 T cell quality and recall responses following an acute viral infection. J Immunol 2010; 185: 4835-4845.
83. Frohlich A, Kisielow J, Schmitz I, Freigang S, Shamshiev AT, Weber J, Marsland BJ, Oxenius A and Kopf M. IL-21R on T cells is critical for sustained functionality and control of chronic viral infection. Science 2009; 324: 15761580.
84. Hinrichs CS, Spolski R, Paulos CM, Gattinoni L, Kerstann KW, Palmer DC, Klebanoff CA, Rosenberg SA, Leonard WJ and Restifo NP. IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy. Blood 2008; 111: 5326-5333.
85. Siegel AM, Heimall J, Freeman AF, Hsu AP, Brittain E, Brenchley JM, Douek DC, Fahle GH, Cohen JI, Holland SM and Milner JD. A critical role for STAT3 transcription factor signaling in the development and maintenance of human T cell memory. Immunity 2011; 35: 806-818.
86. Foulds KE, Rotte MJ and Seder RA. IL-10 is required for optimal CD8 T cell memory following Listeria monocytogenes infection. J Immunol 2006; 177: 2565-2574.
87. Cox JH, Kljavin NM, Ramamoorthi N, Diehl L, Batten M and Ghilardi N. IL-27 promotes T celldependent colitis through multiple mechanisms. J Exp Med 2011; 208: 115-123.
88. Liu JQ, Liu Z, Zhang X, Shi Y, Talebian F, Carl JW Jr, Yu C, Shi FD, Whitacre CC, Trgovcich J and Bai XF. Increased Th17 and regulatory T cell responses in EBV-induced gene 3-deficient mice lead to marginally enhanced development of autoimmune encephalomyelitis. J Immunol 2012; 188: 3099-3106.
89. Wojno ED, Hosken N, Stumhofer JS, O'Hara AC, Mauldin E, Fang Q, Turka LA, Levin SD and Hunter CA. A role for IL-27 in limiting T regulatory cell populations. J Immunol 2011; 187: 266-273.
90. Hall AO, Beiting DP, Tato C, John B, Oldenhove G, Lombana CG, Pritchard GH, Silver JS, Bouladoux N, Stumhofer JS, Harris TH, Grainger J, Wojno ED, Wagage S, Roos DS, Scott P, Turka LA, Cherry S, Reiner SL, Cua D, Belkaid Y, Elloso MM and Hunter CA. The cytokines interleukin 27 and interferon-gamma promote distinct Treg cell populations required to limit infection-induced pathology. Immunity 2012; 37: 511-523.
91. Hirahara K, Ghoreschi K, Yang XP, Takahashi H, Laurence A, Vahedi G, Sciume G, Hall AO, Dupont CD, Francisco LM, Chen Q, Tanaka M, Kanno Y, Sun HW, Sharpe AH, Hunter CA and O'Shea JJ. Interleukin-27 priming of T cells controls IL-17 production in trans via induction of the ligand PD-L1. Immunity 2012; 36: 10171030.
92. Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, Sharpe AH, Freeman GJ and Ahmed R. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 2006; 439: 682-687.
93. Topalian SL, Drake CG and Pardoll DM. Targeting the PD-1/B7-H1 (PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol 2012; 24: 207-212.
94. Zhang J, Tian H, Li C, Cheng L, Zhang S Zhang X, Wang R, Xu F, Dai L, Shi G, Chen X, Li Y, Du T, Deng J, Liu Y, Yang Y, Wei Y and Deng H., Antitumor effects obtained by autologous Lewis lung cancer cell vaccine engineered to secrete mouse Interleukin 27 by means of cationic liposome. Mol Immunol 2013; 55: 26474.