Impact of IL-12 in cancer

Current Cancer Drug Targets

Volumn 17, Issue 8, 2017, Pages 682-697

  Lu, Xinjie ^a  

^a THROMBOSIS RESEARCH INSTITUTE   (United Kingdom)

Author keywords

Cancer; IL 12; Immunotherapy; NK cells; Receptor; Th1 pathway

Indexed keywords

CANCER VACCINE; EPIDERMAL GROWTH FACTOR RECEPTOR 2; GAMMA INTERFERON; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; HYPOXIA INDUCIBLE FACTOR 1ALPHA; INTERLEUKIN 12; INTERLEUKIN 12 RECEPTOR; INTERLEUKIN 12 RECEPTOR BETA1; INTERLEUKIN 12 RECEPTOR BETA2; INTERLEUKIN 12P35; INTERLEUKIN 12P40; INTERLEUKIN 23; INTERLEUKIN 27; INTERLEUKIN 35; SIRTUIN 1; STAT PROTEIN; T LYMPHOCYTE RECEPTOR; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR;

ADAPTIVE IMMUNITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; AUTOPHAGY; CANCER IMMUNOTHERAPY; CANCER RADIOTHERAPY; CANCER THERAPY; CYTOTOXICITY; DOWN REGULATION; HUMAN; IMMUNE RESPONSE; INNATE IMMUNITY; NATURAL KILLER CELL; NEOPLASM; NONHUMAN; OXIDATIVE STRESS; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; T LYMPHOCYTE; TUMOR GROWTH; UPREGULATION; ANIMAL; IMMUNOLOGY; IMMUNOTHERAPY; PROCEDURES;

ADAPTIVE IMMUNITY; ANIMALS; HUMANS; IMMUNITY, INNATE; IMMUNOTHERAPY; INTERLEUKIN-12; NEOPLASMS;

EID: 85038439931     PISSN: 15680096     EISSN: 18735576     Source Type: Journal    
DOI: 10.2174/1568009617666170427102729     Document Type: Review

References (169)

1. Kobayashi, M.; Fitz, L.; Ryan, M.; Hewick, R.M.; Clark, S.C.; Chan, S.; Loudon, R.; Sherman, F.; Perussia, B.; Trinchieri, G. Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J. Exp. Med., 1989, 170, 827-845.
2. Stern, A.S.; Podlaski, F.J.; Hulmes, J.D.; Pan, Y.C.; Quinn, P.M.; Wolitzky, A.G.; Familletti, P.C.; Stremlo, D.L.; Truitt, T.; Chizzonite, R.; Gately, M.K. Purification to homogeneity and partial characterization of cytotoxic lymphocyte maturation factor from human B-lymphoblastoid cells. Proc. Natl. Acad. Sci. U.S.A., 1990, 87, 6808-6812.
3. Germann, T.; Partenheimer, A.; Rüde, E. Requirements for the growth of TH1 lymphocyte clones. Eur. J. Immunol., 1990, 20, 2035-2040.
4. Bork, P.; Holm, L.; Sander, C. The immunoglobulin fold. Structural classification, sequence patterns and common core. J. Mol. Biol., 1994, 242, 309-320.
5. Bazan, J.F. Structural design and molecular evolution of a cytokine receptor superfamily. Proc. Natl. Acad. Sci. U.S.A., 1990, 87, 6934-6938.
6. Yoon, C.; Johnston, S.C.; Tang, J.; Stahl, M.; Tobin, J.F.; Somers, W.S. Charged residues dominate a unique interlocking topography in the heterodimeric cytokine interleukin-12. EMBO. J., 2000, 19, 3530-3541.
7. Lupardus, P.J.; Garcia, K.C. The structure of interleukin-23 reveals the molecular basis of p40 subunit sharing with interleukin-12. J. Mol. Biol., 2008, 382, 931-941.
8. Chua, A.O.; Chizzonite, R.; Desai, B.B.; Truitt, T.P.; Nunes, P.; Minetti, L.J.; Warrier, R.R.; Presky, D.H.; Levine, J.F.; Gately, M.K. Expression cloning of a human IL-12 receptor component. A new member of the cytokine receptor superfamily with strong homology to gp130. J. Immunol., 1994, 153, 128-136.
9. Presky, D.H.; Yang, H.; Minetti, L.J.; Chua, A.O.; Nabavi, N.; Wu, C.Y.; Gately, M.K.; Gubler, U. A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits. Proc. Natl. Acad. Sci. U.S.A., 1996, 93, 14002-14007.
10. Altare, F.; Ensser, A.; Breiman, A.; Reichenbach, J.; Baghdadi, J.E.; Fischer, A.; Emile, J.F.; Gaillard, J.L.; Meinl, E.; Casanova, J.L. Interleukin-12 receptor beta1 deficiency in a patient with abdominal tuberculosis. J. Infect. Dis., 2001, 184, 231-236.
11. Sprecher, C.A.; Grant, F.J.; Baumgartner, J.W.; Presnell, S.R.; Schrader, S.K.; Yamagiwa, T.; Whitmore, T.E.; O’Hara, P.J.; Foster, D.F. Cloning and characterization of a novel class I cytokine receptor. Biochem. Biophys. Res. Commun., 1998, 246, 82-90.
12. Chua, A.; Wilkinson, V.; Presky, D.; Gubler, U. Cloning and characterization of a mouse IL-12 receptor-beta component. J. Immunol., 1995, 155, 4286-4294.
13. de Jong, R.; Altare, F.; Haagen, I.A.; Elferink, D.G.; Boer, T.; van Breda Vriesman, P.J.; Kabel, P.J.; Draaisma, J.M.; van Dissel, J.T.; Kroon, F.P.; Casanova, J.L.; Ottenhoff, T.H. Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients. Science, 1998, 280, 1435-1438.
14. Zou, J.; Presky, D.H.; Wu, C.Y.; Gubler, U. Differential associations between the cytoplasmic regions of the interleukin-12 receptor subunits β1 and β2 and JAK kinases. J. Biol. Chem., 1997, 272, 6073-6077.
15. Parham, C.; Chirica, M.; Timans, J.; Vaisberg, E.; Travis, M.; Cheung, J.; Pflanz, S.; Zhang, R.; Singh, K.P.; Vega, F.; To, W.; Wagner, J.; O’Farrell, A.M.; McClanahan, T.; Zurawski, S.; Hannum, C.; Gorman, D.; Rennick, D.M.; Kastelein, R.A.; de Waal Malefyt, R.; Moore, K.W. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J. Immunol., 2002, 168, 5699-5708.
16. Fujiwara, H.; Hamaoka, T. Antitumor and antimetastatic effects of interleukin 12. Cancer Chemother. Pharmacol., 1996, 38, Suppl:S22-S26.
17. Thomas, E.D.; Meza-Perez, S.; Bevis, K.S.; Randall, T.D.; Gillespie, G.Y.; Langford, C.; Alvarez, R.D. IL-12 Expressing oncolytic herpes simplex virus promotes anti-tumor activity and immunologic control of metastatic ovarian cancer in mice. J. Ovarian Res., 2016, 9, 70.
18. Freytag, S.O.; Barton, K.N.; Zhang, Y. Efficacy of oncolytic adenovirus expressing suicide genes and interleukin-12 in a preclinical model of prostate cancer. Gene Ther., 2013, 20, 1131-1139.
19. Quetglas, J.I.; Labiano, S.; Aznar, M.Á.; Bolaños, E.; Azpilikueta, A.; Rodriguez, I.; Casales, E.; Sánchez-Paulete, A.R.; Segura, V.; Smerdou, C.; Melero, I. Virotherapy with a Semliki Forest Virus-Based Vector Encoding IL12 Synergizes with PD-1/PD-L1 Blockade. Cancer Immunol. Res., 2015, 3, 449-454.
20. Ngiow, S.F.; Young, A.; Blake, S.J.; Hill, G.R.; Yagita, H.; Teng, M.W.; Korman, A.J.; Smyth, M.J. Agonistic CD40 mAb-driven IL12 reverses resistance to anti-PD1 in a T-cell-rich tumor. Cancer Res., 2016, 76, 6266-6277.
21. Zhang, W.; Fulci, G.; Wakimoto, H.; Cheema, T.A.; Buhrman, J.S.; Jeyaretna, D.S.; Stemmer Rachamimov, A.O.; Rabkin, S.D.; Martuza, R.L. Combination of oncolytic herpes simplex viruses armed with angiostatin and IL-12 enhances antitumor efficacy in human glioblastoma models. Neoplasia, 2013, 15, 591-599.
22. Vom Berg, J.; Vrohlings, M.; Haller, S.; Haimovici, A.; Kulig, P.; Sledzinska, A.; Weller, M.; Becher, B. Intratumoral IL-12 combined with CTLA-4 blockade elicits T cell-mediated glioma rejection. J. Exp. Med., 2013, 210, 2803-2811.
23. Wang, X.; Feng, X.; Wang, J.; Shao, N.; Ji, C.; Ma, D.; Henter, J.I.; Fadeel, B.; Zheng, C. Bortezomib and IL-12 produce synergetic anti-multiple myeloma effects with reduced toxicity to natural killer cells. Anticancer Drugs, 2014, 25, 282-288.
24. Ciomber, A.; Smagur, A.; Mitrus, I.; Cichoń, T.; Smolarczyk, R.; Sochanik, A.; Szala, S.; Jarosz, M. Antitumor effects of recombinant antivascular protein ABRaA-VEGF121 combined with IL-12 gene therapy. Arch. Immunol. Ther. Exp. (Warsz), 2014, 62, 161-168.
25. Malvicini, M.; Alaniz, L.; Bayo, J.; Garcia, M.; Piccioni, F.; Fiore, E.; Atorrasagasti, C.; Aquino, J.B.; Matar, P.; Mazzolini, G. Single low-dose cyclophosphamide combined with interleukin-12 gene therapy is superior to a metronomic schedule in inducing immunity against colorectal carcinoma in mice. Oncoimmunology, 2012, 1, 1038-1047.
26. Cao, L.; Zeng, Q.; Xu, C.; Shi, S.; Zhang, Z.; Sun, X. Enhanced antitumor response mediated by the codelivery of paclitaxel and adenoviral vector expressing IL-12. Mol. Pharm., 2013, 10, 1804-1814.
27. Gołb, J.; Zagozdzon, R.; Kamiński, R.; Kozar, K.; Gryska, K.; Izycki, D.; Mackiewicz, A.; Stokłosa, T.; Giermasz, A.; Lasek, W.; Jakóbisiak, M. Potentiatied antitumor effectiveness of combined chemo-immunotherapy with interleukin-12 and 5-fluorouracil of L1210 leukemia. Leukemia, 2001, 15, 613-620.
28. Kozar, K.; Kamiński, R.; Switaj, T.; Ołdak, T.; Machaj, E.; Wysocki, P.J.; Mackiewicz, A.; Lasek, W.; Jakóbisiak, M.; Gołab, J. Interleukin 12-based immunotherapy improves the antitumor effectiveness of a low-dose 5-Aza-2′-deoxycitidine treatment in L1210 leukemia and B16F10 melanoma models in mice. Clin. Cancer Res., 2003, 9, 3124-3133.
29. Zagozdzon, R.; Stokłosa, T.; Gołab, J.; Giermasz, A.; Dabrowska, A.; Lasek, W.; Jakóbisiak, M. Augmented antitumor effects of combination therapy with interleukin-12, cisplatin, and tumor necrosis factor-alpha in a murine melanoma model. Anticancer Res., 1997, 17, 4493-4498.
30. Wigginton, J.M.; Park, J.W.; Gruys, M.E.; Young, H.A.; Jorcyk, C.L.; Back, T.C.; Brunda, M.J.; Strieter, R.M.; Ward, J.; Green, J.E.; Wiltrout, R.H. Complete regression of established spontaneous mammary carcinoma and the therapeutic prevention of genetically programmed neoplastic transition by IL-12/pulse IL-2:induction of local T cell infiltration, Fas/Fas ligand gene expression, and mammary epithelial apoptosis. J. Immunol., 2001, 166, 1156-1168.
31. Osaki, T.; Hashimoto, W.; Gambotto, A.; Okamura, H.; Robbins, P.D.; Kurimoto, M.; Lotze, M.T.; Tahara, H. Potent antitumor effects mediated by local expression of the mature form of the interferon- gamma inducing factor, interleukin-18 (IL-18). Gene Ther., 1999, 6, 808-815.
32. Dabrowska, A.; Giermasz, A.; Gołab, J.; Jakóbisiak, M. Potentiated antitumor effects of interleukin 12 and interferon alpha against B16F10 melanoma in mice. Neoplasma, 2001, 48, 358-361.
33. Yao, L.; Pike, S.E.; Setsuda, J.; Parekh, J.; Gupta, G.; Raffeld, M.; Jaffe, E.S.; Tosato, G. Effective targeting of tumor vasculature by the angiogenesis inhibitors vasostatin and interleukin-12. Blood, 2000, 96, 1900-1905.
34. Helms, M.W.; Prescher, J.A.; Cao, Y.A.; Schaffert, S.; Contag, C.H. IL-12 enhances efficacy and shortens enrichment time in cytokine- induced killer cell immunotherapy. Cancer Immunol. Immunother., 2010, 59, 1325-1334.
35. Yue, T.; Zheng, X.; Dou, Y.; Zheng, X.; Sun, R.; Tian, Z.; Wei, H. Interleukin 12 shows a better curative effect on lung cancer than paclitaxel and cisplatin doublet chemotherapy. BMC Cancer, 2016, 16, 665.
36. El-Shemi, A.G.; Ashshi, A.M.; Na, Y.; Li, Y.; Basalamah, M.; Al-Allaf, F.A.; Oh, E.; Jung, B.K.; Yun, C.O. Combined therapy with oncolytic adenoviruses encoding TRAIL and IL-12 genes markedly suppressed human hepatocellular carcinoma both and in an orthotopic transplanted mouse model. J. Exp. Clin. Cancer Res., 2016, 35, 74.
37. Parhar, R.S.; Zou, M.; Al-Mohanna, F.A.; Baitei, E.Y.; Assiri, A.M.; Meyer, B.F.; Shi, Y. IL-12 immunotherapy of Braf(V600E)- induced papillary thyroid cancer in a mouse model. Lab. Invest., 2016, 96, 89-97.
38. Galvan, D.L.; O’Neil, R.T.; Foster, A.E.; Huye, L.; Bear, A.; Rooney, C.M.; Wilson, M.H. Anti-tumor effects after adoptive transfer of IL-12 transposon-modified murine splenocytes in the OT-I-melanoma mouse model. PLoS One, 2015, 10, e0140744.
39. Kramer, M.G.; Masner, M.; Casales, E.; Moreno, M.; Smerdou, C.; Chabalgoity, J.A. Neoadjuvant administration of Semliki Forest virus expressing interleukin-12 combined with attenuated Salmonella eradicates breast cancer metastasis and achieves long-term survival in immunocompetent mice. BMC Cancer, 2015, 15, 620.
40. Bozeman, E.N.; He, S.; Shafizadeh, Y.; Selvaraj, P. Therapeutic efficacy of PD-L1 blockade in a breast cancer model is enhanced by cellular vaccines expressing B7-1 and glycolipid-anchored IL-12. Hum. Vaccin. Immunother., 2016, 12, 421-30.
41. Bauer, D.F.; Pereboeva, L.; Gillespie, G.Y.; Cloud, G.A.; Elzafarany, O.; Langford, C.; Markert, J.M.; Lamb, L.S. Jr. Effect of HSV-IL12 loaded tumor cell-based vaccination in a mouse model of high-grade neuroblastoma. J. Immunol. Res., 2016, 2016, 2568125.
42. Zhou, Y.; Yoshida, S.; Kubo, Y.; Kobayashi, Y.; Nakama, T.; Yamaguchi, M.; Ishikawa, K.; Nakao, S.; Ikeda, Y.; Ishibashi, T.; Sonoda, K.H. Interleukin-12 inhibits pathological neovascularization in mouse model of oxygen-induced retinopathy. Sci. Rep., 2016, 6, 28140.
43. Freytag, S.O.; Zhang, Y.; Siddiqui, F. Preclinical toxicology of oncolytic adenovirus-mediated cytotoxic and interleukin-12 gene therapy for prostate cancer. Mol. Ther. Oncolytics, 2015, 2, pii:15006.
44. Razi Soofiyani, S.; Kazemi, T.; Lotfipour, F.; Mohammad Hosseini, A.; Shanehbandi, D.; Hallaj-Nezhadi, S.; Baradaran, B. Gene therapy with IL-12 induced enhanced anti-tumor activity in fibrosarcoma mouse model. Artif. Cells Nanomed Biotechnol., 2016, 44, 1988-1993.
45. Yin, P.; Liu, X.; Mansfield, A.S.; Harrington, S.M.; Li, Y.; Yan, Y.; Dong, H. CpG-induced antitumor immunity requires IL-12 in expansion of effector cells and down-regulation of PD-1. Oncotarget, 2016, 7(43), 70223-70231.
46. Yang, S.X.; Wei, W.S.; Ouyan, Q.W.; Jiang, Q.H.; Zou, Y.F.; Qu, W.; Tu, J.H.; Zhou, Z.B.; Ding, H.L.; Xie, C.W.; Lei, Q.M.; Zhong, C.R. Interleukin-12 activated CD8+ T cells induces apoptosis in breast cancer cells and reduces tumor growth. Biomed. Pharmacother., 2016, 84, 1466-1471.
47. Denies, S.; Cicchelero, L.; Van Audenhove, I.; Sanders, N.N. Combination of interleukin-12 gene therapy, metronomic cyclophosphamide and DNA cancer vaccination directs all arms of the immune system towards tumor eradication. J. Cont. Release, 2014, 187, 175-182.
48. Simova, J.; Sapega, O.; Imrichova, T.; Stepanek, I.; Kyjacova, L.; Mikyskova, R.; Indrova, M.; Bieblova, J.; Bubenik, J.; Bartek, J.; Hodny, Z.; Reinis, M. Tumor growth accelerated by chemotherapyinduced senescent cells is suppressed by treatment with IL-12 producing cellular vaccines. Oncotarget, 2016, doi: 10.18632/oncotarget.10712.
49. Paul, W. (Ed.), Fundamental Immunology, Lippincott Williams & Wilkins. 2013, 7th ed. pp. 395-430.
50. Lanier, L.L. Evolutionary struggles between NK cells and viruses. Nat. Rev. Immunol., 2008, 8, 259-268.
51. Long, E.O.; Kim, H.S.; Liu, D.; Peterson, M.E.; Rajagopalan, S. Controlling natural killer cell responses: integration of signals for activation and inhibition. Annu. Rev. Immunol., 2013, 31, 227-258.
52. Romee, R.; Rosario, M.; Berrien-Elliott, M.M.; Wagner, J.A.; Jewell, B.A.; Schappe, T.; Leong, J.W.; Abdel-Latif, S.; Schneider, S.E.; Willey, S.; Neal, C.C.; Yu, L.; Oh, S.T.; Lee, Y.S.; Mulder, A.; Claas, F.; Cooper, M.A.; Fehniger, T.A. Sci. Transl. Med., 2016, 8, 357ra123.
53. Curti, A.; Ruggeri, L.; D’Addio, A.; Bontadini, A.; Dan, E.; Motta, M.R.; Trabanelli, S.; Giudice, V.; Urbani, E.; Martinelli, G.; Paolini, S.; Fruet, F.; Isidori, A.; Parisi, S.; Bandini, G.; Baccarani, M.; Velardi, A.; Lemoli, R.M. Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after in fusion in elderly high risk acute myeloid leukemia patients. Blood, 2011, 118, 3273-3279.
54. Rubnitz, J.E.; Inaba, H.; Ribeiro, R.C.; Pounds, S.; Rooney, B.; Bell, T.; Pui, C.H.; Leung, W. NKAML: A pilot study to determine the safety and feasibility of haploidentical natural killer cell transplantation in childhood acute myeloid leukemia. J. Clin. Oncol., 2010, 28, 955-959.
55. Bandini, G.; Bonifazi, F.; Lewis, R.E.; Cavo, M.; Velardi, A.; Lemoli, R.M. Larger size of donor alloreactive NK cell repertoire correlates with better response to NK cell immunotherapy in elderly acute myeloid leukemia patients. Clin. Cancer Res., 2016, 22, 1914-1921.
56. Robertson, M.J.; Ritz, J. Biology and clinical relevance of human natural killer cells. Blood, 1990, 76, 2421-2438.
57. Dunn, G.P.; Koebel, C.M.; Schreiber, R.D. Interferons, immunity and cancer immunoediting. Nat. Rev. Immunol., 2006, 6, 836-848.
58. Curti, A.; Parenza, M.; Colombo, M.P. Autologous and MHC class I-negative allogeneic tumor cells secreting IL-12 together cure disseminated A20 lymphoma. Blood, 2003, 101, 568-575.
59. Eisenring, M.; vom Berg, J.; Kristiansen, G.; Saller, E.; Becher, B. IL-12 initiates tumor rejection lymphoid tissue-inducer cells bearing the natural cytotoxicity receptor NKp46. Nat. Immunol. 2010, 11, 1030-1038.
60. Nakajima, C.; Uekusa, Y.; Iwasaki, M.; Yamaguchi, N.; Mukai, T.; Gao, P.; Tomura, M.; Ono, S.; Tsujimura, T.; Fujiwara, H.; Hamaoka, T. A role of interferon-gamma (IFN-gamma) in tumor immunity:T cells with the capacity to reject tumor cells are generated but fail to migrate to tumor sites in IFN-gamma-deficient mice. Cancer Res., 2001, 61, 3399-3405.
61. Goplen, N.P.; Saxena, V.; Knudson, K.M.; Schrum, A.G.; Gil, D.; Daniels, M.A.; Zamoyska, R.; Teixeiro, E. IL-12 Signals through the TCR To Support CD8 Innate Immune Responses. J. Immunol., 2016, 197, 2434-2443.
62. Yamada, E.; Okada, S.; Bastie, C.C.; Vatish, M.; Nakajima, Y.; Shibusawa, R.; Ozawa, A.; Pessin, J.E.; Yamada, M. Fyn phosphorylates AMPK to inhibit AMPK activity and AMP-dependent activation of autophagy. Oncotarget, 2016, 7, 74612-74629.
63. Jeong, K.Y.; Lee, E.J.; Kim, S.J.; Yang, S.H.; Sung, Y.C.; Seong, J. Irradiation-induced localization of IL-12-expressing mesenchymal stem cells to enhance the curative effect in murine metastatic hepatoma. Int. J. Cancer, 2015, 137, 721-730.
64. Carson, W.E.; Parihar, R.; Lindemann, M.J.; Personeni, N.; Dierksheide, J.; Meropol, N.J.; Baselga, J.; Caligiuri, M.A. Interleukin-2 enhances the natural killer cell response to Herceptin-coated Her2/neu-positive breast cancer cells. Eur. J. Immunol., 2001, 31, 3016-3025.
65. Lieberman, M.D.; Sigal, R.K.; Williams, N.N. 2nd; Daly, J.M. Natural killer cell stimulatory factor (NKSF) augments natural killer cell and antibody-dependent tumoricidal response against colon carcinoma cell lines. J. Surg. Res., 1991, 50, 410-415.
66. Yu, J.; Wei, M.; Becknell, B.; Trotta, R.; Liu, S.; Boyd, Z.; Jaung, M.S.; Blaser, B.W.; Sun, J.; Benson, D.M. Jr; Mao, H.; Yokohama, A.; Bhatt, D.; Shen, L.; Davuluri, R.; Weinstein, M.; Marcucci, G.; Caligiuri, M.A. Pro- and antiinflammatory cytokine signaling:reciprocal antagonism regulates interferon-gamma production by human natural killer cells. Immunity, 2006, 24, 575-590.
67. Sarhan, D.; Palma, M.; Mao, Y.; Adamson, L.; Kiessling, R.; Mellstedt, H.; Österborg, A.; Lundqvist, A. Dendritic cell regulation of NK-cell responses involves lymphotoxin-α, IL-12, and TGF-β. Eur. J. Immunol., 2015, 45, 1783-1793.
68. Liu, G.; Bi, Y.; Xue, L.; Zhang, Y.; Yang, H.; Chen, X.; Lu, Y.; Zhang, Z.; Liu, H.; Wang, X.; Wang, R.; Chu, Y.; Yang, R. Dendritic cell SIRT1-HIF1α axis programs the differentiation of CD4+ T cells through IL-12 and TGF-β1. Proc. Natl. Acad. Sci. U.S.A., 2015, 112, E957-E965.
69. Jin, J.; Xie, X.; Xiao, Y.; Hu, H.; Zou, Q.; Cheng, X.; Sun, S.C. Epigenetic regulation of the expression of Il12 and Il23 and autoimmune inflammation by the deubiquitinase Trabid. Nat. Immunol., 2016, 17, 259-268.
70. Braun, M.; Ress, M.L.; Yoo, Y.E.; Scholz, C.J.; Eyrich, M.; Schlegel, P.G.; Wölfl, M. IL12-mediated sensitizing of T-cell receptor- dependent and -independent tumor cell killing. Oncoimmunology, 2016, 5, e1188245.
71. Rölle, A.; Brodin, P. Immune Adaptation to Environmental Influence:The Case of NK Cells and HCMV. Trends Immunol., 2016, 37, 233-243.
72. Rölle, A.; Pollmann, J.; Ewen, E.M.; Le, V.T.; Halenius, A.; Hengel, H.; Cerwenka, A. IL-12-producing monocytes and HLA-E control HCMV-driven NKG2C+ NK cell expansion. J. Clin. Invest., 2014, 124, 5305-5316.
73. Fang, S.; Wang, Y.; Chun, Y.S.; Liu, H.; Ross, M.I.; Gershenwald, J.E.; Cormier, J.N.; Royal, R.E.; Lucci, A.; Schacherer, C.W.; Reveille, J.D.; Sui, D.; Bassett, R.L.Jr.; Wang, L.E.; Wei, Q.; Amos, C.I.; Lee, J.E. The relationship between blood IL-12p40 level and melanoma progression. Int. J. Cancer, 2015, 136, 1874-1880.
74. Youssef, S.S.; Mohammad, M.M.; Ezz-El-Arab, L.R. Clinical significance of serum IL-12 level in patients with early breast carcinoma and its correlation with other tumor markers. Open Access Maced. J. Med. Sci., 2015, 3, 640-644.
75. Zitvogel, L.; Kroemer, G. CD103+ dendritic cells producing interleukin-12 in anticancer immunosurveillance. Cancer Cell, 2014, 26, 591-593.
76. Takeda, Y.; Azuma, M.; Matsumoto, M.; Seya, T. Tumoricidal efficacy coincides with CD11c up-regulation in antigen-specific CD8(+) T cells during vaccine immunotherapy. J. Exp. Clin. Cancer Res., 2016, 35, 143.
77. Makino, Y.; Kanno, R.; Ito, T.; Higashino, K.; Taniguchi, M. Predominant expression of invariant V alpha 14+ TCR alpha chain in NK1.1+ T cell populations. Int. Immunol., 1995, 7, 1157-1161.
78. Godfrey, D.I.; MacDonald, H.R.; Kronenberg, M.; Smyth, M.J.; Van Kaer, L. NKT cells: What’s in a name? Nat. Rev. Immunol., 2004, 4, 231-237.
79. Kawano, T.; Cui, J.; Koezuka, Y.; Toura, I.; Kaneko, Y.; Motoki, K.; Ueno, H.; Nakagawa, R.; Sato, H.; Kondo, E.; Koseki, H.; Taniguchi, M. CD1d-restricted and TCR-mediated activation of V alpha14 NKT cells by glycosylceramides. Science, 1997, 278, 1626-1629.
80. Kitamura, H.; Iwakabe, K.; Yahata, T.; Nishimura, S.; Ohta, A.; Ohmi, Y.; Sato, M.; Takeda, K.; Okumura, K.; Van Kaer, L.; Kawano, T.; Taniguchi, M.; Nishimura, T. The natural killer T (NKT) cell ligand alpha-galactosylceramide demonstrates its immunopotentiating effect by inducing interleukin (IL)-12 production by dendritic cells and IL-12 receptor expression on NKT cells. J. Exp. Med., 1999, 189, 1121-1128.
81. Tomihara, K.; Kato, K.; Masuta, Y.; Nakamura, K.; Tanaka, T.; Hiratsuka, H.; Hamada, H. Gene transfer of the CD40-ligand to human dendritic cells induces NK-mediated antitumor effects against human carcinoma cells. Int. J. Cancer, 2007, 120, 1491-1498.
82. Kalos, M.; Levine, B.L.; Porter, D.L.; Katz, S. Grupp, S.A.; Bagg, A.; June, C.H. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci. Transl. Med., 2011, 3, 95ra73.
83. Brentjens, R.J.; Santos, E.; Nikhamin, Y.; Yeh, R.; Matsushita, M.; La Perle, K.; Quintás-Cardama, A.; Larson, S.M.; Sadelain, M. Genetically targeted T cells eradicate systemic acute lymphoblastic leukemia xenografts. Clin. Cancer Res., 2007, 13, 5426-5435.
84. June, C.; Rosenberg, S.A.; Sadelain, M.; Weber, J.S. T-cell therapy at the threshold. Nat. Biotechnol., 2012, 30, 611-614.
85. Sadelain, M. Chimeric antigen receptors: driving immunology towards synthetic biology. Curr. Opin. Immunol., 2016, 41, 68-76.
86. Chmielewski, M.; Kopecky, C.; Hombach, A.A.; AbkenH. IL-12 release by engineered T cells expressing chimeric antigen receptors can effectively Muster an antigen-independe nt macrophage response on tumor cells that have shut down tumor antigen expression. Cancer Res., 2011, 71, 5697-5706.
87. Pegram, H.J.; Lee, J.C.; Hayman,; Imperato, G.H.; Tedder, T.F.; Sadelain, M.; Brentjens, R.J. Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning. Blood, 2012, 119, 4133-4141.
88. Kerkar, S.P.; Muranski, P.; Kaiser, A.; Boni, A.; Sanchez-Perez, L.; Yu, Z.; Palmer, D.C.; Reger, R.N.; Borman, Z.A.; Zhang, L.; Morgan, R.A.; Gattinoni, L.; Rosenberg, S.A.; Trinchieri, G.; Restifo, N.P. Tumor-specific CD8+ T cells expressing interleukin-12 eradicate established cancers in lymphodepleted hosts. Cancer Res., 2010, 70, 6725-6734.
89. Kerkar, S.P.; Goldszmid, R.S.; Muranski, P.; Chinnasamy, D.; Yu, Z.; Reger, R.N.; Leonardi, A.J.; Morga,n R.A.; Wang, E.; Marincola, F.M.; Trinchieri, G.; Rosenberg, S.A.; Restifo, N.P. IL-12 triggers a programmatic change in dysfunctional myeloid-derived cells within mouse tumors. J. Clin. Invest., 2011, 121, 4746-4757.
90. Vetter, M.; Hofer, M.J.; Roth, E.; Pircher, H.P.; Pagenstecher, A. Intracerebral interleukin 12 induces glioma rejection in the brain predominantly by CD8+ T cells and independently of interferongamma. J. Neuropathol. Exp. Neurol., 2009, 68, 525-534.
91. Vom Berg, J.; Vrohlings, M.; Haller, S.; Haimovici, A.; Kulig, P.; Sledzinska, A.; Weller, M.; Becher, B. Intratumoral IL-12 combined with CTLA-4 blockade elicits T cell-mediated glioma rejection. J. Exp. Med., 2013, 210, 2803-2811.
92. Gerber, S.A.; Moran, J.P.; Frelinger, J.G. Frelinger, J.A.; Fenton, B.M.; Lord, E.M. Mechanism of IL-12 mediated alterations in tumour blood vessel morphology: analysis using whole-tissue mounts. Br. J. Cancer, 2003, 88, 1453-1461.
93. Sorensen, E.W.; Gerber, S.A.; Frelinger, J.G.; Lord, E.M. IL-12 suppresses vascular endothelial growth factor receptor 3 expression on tumor vessels by two distinct IFN-gamma-dependent mechanisms. J Immunol., 2010, 184, 1858-1866.
94. Seder, R.A.; Interleukin 12 acts directly on CD4+ T cells to enhance priming for interferon gamma production and diminishes interleukin 4 inhibition of such priming. Proc. Natl. Acad. Sci. USA, 1993, 90, 10188-10192.
95. Hsieh, C.S. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science, 1993, 260, 547-549.
96. Manetti, R. Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specimmune responses and inhibits the development of IL-4-producing Th cells. J. Exp. Med., 1993, 177, 1199-1204.
97. Swain, S.L. Characterization of T helper 1 and 2 cell subsets in normal mice. Helper T cells responsible for IL-4 and IL-5 production are present as precursors that require priming before they develop into lymphokine-secreting cells. J. Immunol., 1988, 141, 3445-3455.
98. Betz, M. Regulation and development of cytochrome c-specific IL-4-producing T cells. J. Immunol., 1990, 145, 1046-1052.
99. Kopf, M.; Le Gros, G.; Bachmann, M.; Lamers, M.C.; Bluethmann, H.; Köhler, G. Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature, 1993, 362, 245-248.
100. Sornasse, T. Differentiation and stability of T helper 1 and 2 cells derived from naive human neonatal CD4+ T cells, analyzed at the single-cell level. J. Exp. Med., 1996, 184, 473-483.
101. Schmitt, N.; Bustamante, J.; Bourdery, L.; Bentebibel, S.E.; Boisson-Dupuis, S.; Hamlin, F.; Tran, M.V.; Blankenship, D.; Pascual, V.; Savino, D.A.; Banchereau, J.; Casanova, J.L.; Ueno, H. IL-12 receptor beta1 deficiency alters T follicular helper cell response in humans. Blood, 2013, 121, 3375-3385.
102. Chowdhury, F.Z.; Ramos, H.J.; Davis, L.S.; Forman, J.; Farrar, J.D. IL-12 selectively programs effector pathways that are stably expressed in human CD8+ effector memory T cells. Blood, 2011, 118, 3890-3900.
103. Zhang, L.; Kerkar, S.P.; Yu, Z.; Zheng, Z.; Yang, S.; Restifo, N.P.; Rosenberg, S.A.; Morgan, R.A. Improving adoptive T cell therapy by targeting and controlling IL-12 expression to the tumor environment. Mol. Ther., 2011, 19, 751-759.
104. Tatsumi, T.; Huang, J.; Gooding, W.E.; Gambotto, A.; Robbins, P.D.; Vujanovic, N.L.; Alber, S.M.; Watkins, S.C.; Okada, H.; Storkus, W.J. Intratumoural delivery of dendritic cells engineered to secrete both interleukin (IL)-12 and IL-18 effectively treats local and distant disease in association with broadly reactive Tc1-type immunity. Cancer Res., 2003, 63, 6378-6386.
105. Hung, K.; Hayashi, R.; Lafond-Walker, A.; Lowenstein, C.; Pardoll, D.; Levitsky, H. The central role of CD4(+) T cells in the antitumour immune response. J. Exp. Med., 1998, 188, 2357-2368.
106. Prigione, I.; Covone, A.E.; Giacopelli, F.; Bocca, P.; Risso, M.; Tripodi, G.; Pistorio, A.; Sozzi, G.; Airoldi, I.; Ravazzolo, R.; Pistoia, V. IL12RB2 Polymorphisms correlate with risk of lung adenocarcinoma. Immunobiology, 2016, 221, 291-299.
107. Peng, Q.; Li, S.; Lao, X.; Chen, Z.; Li, R.; Qin, X. Interleukin-12B+1188A/C polymorphism contributes to increased hepatocellular carcinoma susceptibility: evidence from a meta-analysis. Clin. Res. Hepatol. Gastroenterol., 2014, 38, 735-743.
108. Navaglia, F.; Basso, D.; Zambon, C.F.; Ponzano, E.; Caenazzo, L.; Gallo, N.; Falda, A.; Belluco, C.; Fogar, P.; Greco, E.; Di Mario, F.; Rugge, M.; Plebani, M. Interleukin 12 gene polymorphisms enhance gastric cancer risk in H pylori in ected individuals. J. Med. Genet., 2005, 42, 503-510.
109. Kaarvatn, M.H.; Vrbanec, J.; Kulic, A.; Knezevic, J.; Petricevic, B.; Balen, S.; Vrbanec, D.; Dembic, Z. Single nucleotide polymorphism in the interleukin 12B gene is associated with risk for breast cancer development. Scand. J. Immunol., 2012, 76, 329-335.
110. Fang, S.; Wang, Y.; Chun, Y.S.; Liu, H.; Ross, M.I.; Gershenwald, J.E.; Cormier, J.N.; Royal, R.E.; Lucci, A.; Schacherer, C.W.; Reveille, J.D.; Chen, W.; Sui, D.; Bassett, R.L.; Wang, L.E.; Wei, Q.; Amos, C.I.; Lee, J.E. Association of common genetic polymorphisms with melanoma patient IL-12p40 blood levels, risk, and outcomes. J. Invest. Dermatol., 2015, 135, 2266-2272.
111. Hussain, S.K.; Madeleine, M.M.; Johnson, L.G.; Du, Q.; Galloway, D.A.; Daling, J.R.; Malkki, M.; Petersdorf, E.W.; Schwartz, S.M. Nucleotide variation in IL-10 and IL-12 and their receptors and cervical and vulvar cancer risk: a hybrid case-parent triad and casecontrol study. Int. J. Cancer, 2013, 133, 201-213.
112. Boggio, K.; Di Carlo, E.; Rovero, S.; Cavallo, F.; Quaglino, E.; Lollini, P.L.; Nanni, P.; Nicoletti, G.; Wolf, S.; Musiani, P.; Forni, G. Ability of systemic interleukin-12 to hamper progressive stages of mammary carcinogenesis in HER2/neu transgenic mice. Cancer Res., 2000, 60, 359-364.
113. Smyth, M.J.; Taniguchi, M.; Street, S.E. The anti-tumor activity of IL-12: mechanisms of innate immunity that are model and dose dependent. J. Immunol., 2000, 165, 2665-2670.
114. Alatrash, G.; Hutson, T.E.; Molto, L.; Richmond, A.; Nemec, C.; Mekhail, T.; Elson, P.; Tannenbaum, C.; Olencki, T.; Finke, J.; Bukowski, R.M. Clinical and immunologic effects of subcutaneously administered interleukin-12 and interferon alfa-2b:phase I trial of patients with metastatic renal cell carcinoma or malignant melanoma. J. Clinl. Oncol., 2004, 22, 2891-2900.
115. Motzer, R.J.; Rakhit, A.; Thompson, J.A.; Nemunaitis, J.; Murphy, B.A.; Ellerhorst, J.; Schwartz, L.H.; Berg, W.J.; Bukowski, R.M. Randomized multicenter phase II trial of subcutaneous recombinant human interleukin-12 versus interferon-alpha 2a for patients with advanced renal cell carcinoma. J. Interferon Cytokine Res., 2001, 21, 257-263.
116. Gollob, J.A.; Mier, J.W.; Veenstra, K.; McDermott, D.F.; Clancy, D.; Clancy, M.; Atkins, M.B. Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: ability to maintain IFN-gamma induction is associated with clinical response. Clin. Cancer Res., 2000, 6, 1678-1692.
117. Bajetta, E.; Del Vecchio, M.; Mortarini, R.; Nadeau, R.; Rakhit, A.; Rimassa, L.; Fowst, C.; Borri, A.; Anichini, A.; Parmiani, G. Pilot study of subcutaneous recombinant human interleukin 12 in metastatic melanoma. Clin. Cancer Res., 1998, 4, 75-85.
118. Cebon, J.; Jäger, E.; Shackleton, M.J.; Gibbs, P.; Davis, I.D.; Hopkins, W.; Gibbs, S.; Chen, Q.; Karbach, J.; Jackson, H.; MacGregor, D.P.; Sturrock, S.; Vaughan, H.; Maraskovsky, E.; Neumann, A.; Hoffman, E.; Sherman, M.L.; Knuth, A. Two phase I studies of low dose recombinant human IL-12 with Melan-A and influenza peptides in subjects with advanced malignant melanoma. Cancer Immun. 2003, 3, 7.
119. Daud, A.I.; DeConti, R.C.; Andrews, S.; Urbas, P.; Riker, A.I.; Sondak, V.K.; Munster, P.N.; Sullivan, D.M.; Ugen, K.E.; Messina, J.L.; Heller, R. Phase I trial of interleukin-12 plasmid electroporation in patients with metastatic melanoma. J. Clin. Oncol., 2008, 26, 5896-5903.
120. Heinzerling, L.; Burg, G.; Dummer, R.; Maier, T.; Oberholzer, P.A.; Schultz, J.; Elzaouk, L.; Pavlovic, J.; Moelling, K. Intratumoral injection of DNA encoding human interleukin 12 into patients with metastatic melanoma: clinical efficacy. Hum. Gene Ther., 2005, 16, 35-48.
121. Mahvi, D.M.; Henry, M.B.; Albertini, M.R.; Weber, S.; Meredith, K.; Schalch, H.; Rakhmilevich, A.; Hank, J.; Sondel, P. Intratumoral injection of IL-12 plasmid DNA-results of a phase I/IB clinical trial. Cancer Gene Ther., 2007, 14, 717-723.
122. Triozzi, P.L.; Allen, K.O.; Carlisle, R.R.; Craig, M.; LoBuglio, A.F.; Conry, R.M. Phase I study of the intratumoral administration of recombinant canarypox viruses expressing B7.1 and interleukin 12 in patients with metastatic melanoma. Clin. Cancer Res., 2005, 11, 4168-4175.
123. Rudman, S.M.; Jameson, M.B.; McKeage, M.J.; Savage, P.; Jodrell, D.I.; Harries, M.; Acton, G.; Erlandsson, F.; Spicer, J.F. A phase 1 study of AS1409, a novel antibody-cytokine fusion protein, in patients with malignant melanoma or renal cell carcinoma. Clin. Cancer Res., 2011, 17, 1998-2005.
124. Bekaii-Saab, T.S.; Roda, J.M.; Guenterberg, K.D.; Ramaswamy, B.; Young, D.C.; Ferketich, A.K.; Lamb, T.A.; Grever, M.R.; Shapiro, C.L.; Carson, W.E. 3rd; A phase I trial of paclitaxel and trastuzumab in combination with interleukin-12 in patients with HER2/neu-expressing malignancies. Mol. Cancer Ther., 2009, 8, 2983-2991.
125. Hurteau, J.A.; Blessing, J.A.; DeCesare, S.L.; Creasman, W.T. Evaluation of recombinant human interleukin-12 in patients with recurrent or refractory ovarian cancer: a gynecologic oncology group study. Gynecol. Oncol., 2001, 82, 7-10.
126. Alvarez, R.D.; Sill, M.W.; Davidson, S.A.; Muller, C.Y.; Bender, D.P.; DeBernardo, R,L,; Behbakht, K.; Huh, W.K. A phase II trial of intraperitoneal EGEN-001, an IL-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer: A Gynecologic Oncology Group study. Gynecol. Oncol., 2014, 133, 433-438.
127. Lacy, M.Q.; Jacobus, S.; Blood, E.A.; Kay, N.E.; Rajkumar, S.V.; Greipp, P.R. Phase II study of interleukin-12 for treatment of plateau phase multiple myeloma (E1A96): A trial of the Eastern Cooperative Oncology Group. Leuk. Res., 2009, 33, 1485-1489.
128. Rook, A.H.; Wood, G.S.; Yoo, E.K.; Elenitsas, R.; Kao, D.M.; Sherman, M.L.; Witmer, W.K.; Rockwell, K.A.; Shane, R.B.; Lessin, S.R.; Vonderheid, E.C. Interleukin-12 therapy of cutaneous T-cell lymphoma induces lesion regression and cytotoxic T-cell responses. Blood, 1999, 94, 902-908.
129. Duvic, M.; Sherman, M.L.; Wood, G.S.; Kuzel, T.M.; Olsen, E.; Foss, F.; Laliberté, R.J.; Ryan, J.L.; Zonno, K.; Rook, A.H. A phase II open-label study of recombinant human interleukin-12 in patients with stage IA, IB, or IIA mycosis fungoides. J. Am. Acad. Dermatol., 2006, 55, 807-813.
130. Younes, A.; Pro, B.; Robertson, M.J.; Flinn, I.W.; Romaguera, J.E.; Hagemeister, F.; Dang, N.H.; Fiumara, P.; Loyer, E.M.; Cabanillas, F.F.; McLaughlin, P.W.; Rodriguez, M.A.; Samaniego, F. Phase II clinical trial of interleukin-12 in patients with relapsed and refractory non-Hodgkin’s lymphoma and Hodgkin’s disease. Clin. Cancer Res., 2004, 10, 5432-5438.
131. Ansell, S.M.; Witzig, T.E.; Kurtin, P.J.; Sloan, J.A.; Jelinek, D.F.; Howell, K.G.; Markovic, S.N.; Habermann, T.M.; Klee, G.G.; Atherton, P.J.; Erlichman, C. Phase 1 study of interleukin-12 in combination with rituximab in patients with B-cell non-Hodgkin lymphoma. Blood, 2002, 99, 67-74.
132. Sangro, B.; Mazzolini, G.; Ruiz, J.; Herraiz, M.; Quiroga, J.; Herrero, I.; Benito, A.; Larrache, J.; Pueyo, J.; Subtil, J.C.; Olagüe, C.; Sola, J.; Sádaba, B.; Lacasa, C.; Melero, I.; Qian, C.; Prieto, J. Phase I trial of intratumoral injection of an adenovirus encoding interleukin-12 for advanced digestive tumors. J. Clin. Oncol., 2004, 22, 1389-1397.
133. Zhang, L.; Morgan, R.A.; Beane, J.D.; Zheng, Z.; Dudley, M.E.; Kassim, S.H.; Nahvi, A.V.; Ngo, L.T.; Sherry, R.M.; Phan, G.Q.; Hughes, M.S.; Kammula, U.S.; Feldman, S.A.; Toomey, M.A.; Kerkar, S.P.; Restifo, N.P.; Yang, J.C, Rosenberg, S.A. Tumorinfiltrating lymphocytes genetically engineered with an inducible gene encoding interleukin-12 for the immunotherapy of metastatic melanoma. Clin. Cancer Res., 2015, 21, 2278-2288.
134. Jiang, C.; Magee, D.M.; Cox, R. Construction of a single-chain interleukin-12-expressing retroviral vector and its application in cytokine gene therapy against experimental coccidiomycosis. Infect. Immun., 1999, 67, 2996-3001.
135. Cicchelero, L.; Denies, S.; Haers, H.; Vanderperren, K.; Stock, E.; Van Brantegem, L.; de Rooster, H.; Sanders, N.N. Intratumoural interleukin 12 gene therapy stimulates the immune system and decreases angiogenesis in dogs with spontaneous cancer. Vet. Comp. Oncol., 2016, doi: 10.1111/vco.12255.
136. Cutrera, J.; King, G.; Jones, P.; Kicenuik, K.; Gumpel, E.; Xia, X.; Li, S. Safe and effective treatment of spontaneous neoplasms with interleukin 12 electro-chemo-gene therapy. J. Cell Mol. Med., 2015, 19, 664-675.
137. Mirjačić Martinović, K.; Babović, N.; Džodić, R.; Jurišić, V.; Matković, S.; Konjević, G. Favorable effects of combined IL-12 and IL-18 treatment on NK cell cytotoxicity and CD25 receptor expression in metastatic melanoma patients. J. Transl. Med., 2015, 13, 120.
138. Cicchelero, L.; Denies, S.; Vanderperren, K.; Stock, E.; Van Brantegem, L.; de Rooster, H.; Sanders, N.N. Immunological, antiangiogenic and clinical effects of intratumoral interleukin 12 electrogene therapy combined with metronomic cyclophosphamide in dogs with spontaneous cancer: A pilot study. Cancer Lett., 2017, 400, 205-218.
139. Ni, J.; Hölsken, O.; Miller, M.; Hammer, Q.; Luetke-Eversloh, M.; Romagnani, C.; Cerwenka, A. Adoptively transferred natural killer cells maintain long-term antitumor activity by epigenetic imprinting and CD4+ T cell help. Oncoimmunology, 2016, 5, e1219009.
140. van Herpen, C.M.; Looman, M.; Zonneveld, M.; Scharenborg, N.; de Wilde, P.C.; van de Locht, L.; Merkx, M.A.; Adema, G.J.; de Mulder, P.H. Intratumoral administration of recombinant human interleukin 12 in head and neck squamous cell carcinoma patients elicits a T-helper 1 profile in the locoregional lymph nodes. Clin. Cancer Res., 2004, 10, 2626-2635.
141. Kishima, H.; Shimizu, K.; Miyao, Y.; Mabuchi, E.; Tamura, K.; Tamura, M.; Sasaki, M.; Hakakawa, T. Systemic interleukin 12 displays anti-tumour activity in the mouse central nervous system Br. J. Cancer, 1998, 78, 446-453.
142. Joki, T.; Kikuchi, T.; Akasaki, Y.; Saitoh, S.; Abe, T.; Ohno, T. Induction of effective antitumor immunity in a mouse brain tumor model using B7-1 (CD80) and intercellular adhesive molecule 1 (ICAM-1; CD54) transfection and recombinant interleukin 12. Int. J. Cancer, 1999, 82, 714-720.
143. Kikuchi, T.; Joki, T.; Akasaki, Y.; Abe, T.; Ohno, T. Induction of antitumor immunity using intercellular adhesion molecule 1 (ICAM-1) transfection in mouse glioma cells. Cancer Lett., 1999, 142, 201-206.
144. Lissoni, P.; Rovelli, F.; Fumagalli, L.; Mauri, E.; Barni, S.; Tancini, G. Increased blood concentrations of interleukin-12 are associated with a longer survival in untreatable metastatic solid tumor patients: preliminary observations. Int. J. Biol. Markers, 1997, 12, 125-127.
145. Hussein, M.Z.; Al Fikky, A.; Abdel Bar, I.; Attia, O. Serum IL-6 and IL-12 levels in breast cancer patients. Egypt J. Immunol., 2004, 11, 165-170.
146. Chavey, C.; Bibeau, F.; Gourgou-Bourgade, S.; Burlinchon, S.; Boissière, F.; Laune, D.; Roques, S.; Lazennec, G. Oestrogen receptor negative breast cancers exhibit high cytokine content. Breast Cancer Res., 2007, 9, R15.
147. Barrera, L.; Montes-Servín, E.; Barrera, A.; Ramírez-Tirado, L.A.; Salinas-Parra, F.; Bañales-Méndez, J.L.; Sandoval-Ríos, M.; Arrieta, Ó. Cytokine profile determined by data-mining analysis set into clusters of non-small-cell lung cancer patients according to prognosis. Ann. Oncol., 2015, 26, 428-435.
148. Tazaki, E.; Shimizu, N.; Tanaka, R.; Yoshizumi, M.; Kamma, H.; Imoto, S.; Goya, T.; Kozawa, K.; Nishina, A.; Kimura, H. Serum cytokine profiles in patients with prostate carcinoma. Exp. Ther. Med., 2011, 2, 887-891.
149. Enewold, L.; Mechanic, L.E.; Bowman, E.D.; Zheng, Y.L.; Yu, Z.; Trivers, G.; Alberg, A.J.; Harris, C.C. Serum concentrations of cytokines and lung cancer survival in African Americans and Caucasians. Cancer Epidemiol. Biomarkers Prev., 2009, 18, 215-222.
150. Naeger, L.; McKinney, J.; Salvekar, A.; Hoey, T. Identification of a STAT4 binding site in the interleukin-12 receptor required for signaling. J. Biol. Chem., 1999, 274, 1875-1878.
151. Nishikomori, R.; Usui, T.; Wu, C.Y.; Morinobu, A.; O’Shea, J.J.; Strober, W. Activated STAT4 has an essential role in Th1 differentiation and proliferation that is independent of its role in the maintenance of IL-12R beta 2 chain expression and signaling. J. Immunol., 2002, 169, 4388-4398.
152. Yamamoto, K.; Yamaguchi, M.; Miyasaka, N.; Miura, O. SOCS-3 inhibits IL-12-induced STAT4 activation by binding through its SH2 domain to the STAT4 docking site in the IL-12 receptor beta2 subunit. Biochem. Biophys. Res. Commun., 2003, 310, 1188-1193.
153. Yamamoto, K.; Quelle, F.W.; Thierfelder, W.E.; Kreider, B.L.; Gilbert, D.J.; Jenkins, N,A.; Copeland, N.G.; Silvennoinen, O.; Ihle, J.N. Stat4, a novel gamma interferon activation site-binding protein expressed in early myeloid differentiation. Mol. Cell Biol., 1994, 14, 4342-4349.
154. Wurster, A.L.; Tanaka, T.; Grusby, M.J. The biology of Stat4 and Stat6. Oncogene, 2000, 19, 2577-2584.
155. Thierfelder, W.E. Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells. Nature, 1996, 382, 171.
156. Shimoda, K.; Kato, K.; Aoki, K.; Matsuda, T.; Miyamoto, A.; Shibamori, M.; Yamashita, M.; Numata, A.; Takase, K.; Kobayashi, S.; Shibata, S.; Asano, Y.; Gondo, H.; Sekiguchi, K.; Nakayama, K.; Nakayama, T.; Okamura, T.; Okamura, S.; Niho, Y.; Nakayama, K. Tyk2 plays a restricted role in IFN alpha signaling, although it is required for IL-12- mediated T cell function. Immunity, 2000, 13, 561-571.
157. Karaghiosoff, M.; Neubauer, H.; Lassnig, C.; Kovarik, P.; Schindler, H.; Pircher, H.; McCoy, B.; Bogdan, C.; Decker, T.; Brem, G.; Pfeffer, K.; Müller, M. Partial impairment of cytokine responses in Tyk2-deficient mice. Immunity, 2000, 13, 549-560.
158. Curtsinger, J.M.; and Mescher, M.F. Inflammatory cytokines as a third signal for T cell activation. Curr. Opin. Immunol., 2010, 22, 333-340.
159. Stevens, C.N.; Simeone, A.M.; John, S.; Ahmed, Z.; Lucherini, O.M.; Baldari, C.T.; Ladbury, J.E. T-cell receptor early signalling complex activation in response to interferon-alpha receptor stimulation. Biochem. J. 2010, 428, 429-437.
160. Uddin, S.; Sher, D.A.; Alsayed, Y.; Pons, S.; Colamonici, O.R.; Fish, E.N.; White, M.F.; Platanias, L.C. Interaction of p59fyn with interferonactivated Jak kinases. Biochem. Biophys. Res. Commun., 1997, 235, 83-88.
161. van’t Hof, W.; Resh, M.D. Dual fatty acylation of p59 (Fyn) is required for association with the T cell receptor zeta chain through phosphotyrosine-Src homology domain-2 interactions. J. Cell Biol., 1999, 145, 377-389.
162. Gascoigne, N.R.; Casas, J.; Brzostek, J.; Rybakin, V. Initiation of TCR phosphorylation and signal transduction. Front Immunol., 2011, 2, 72.
163. Minguet, S.; Swamy, M.; Alarcón, B.; Luescher, I.F.; Schamel, W.W. Full activation of the T cell receptor requires both clustering and conformational changes at CD3. Immunity, 2007, 26, 43-54.
164. Markiewicz, M.A.; Wise, E.L.; Buchwald, Z.S.; Cheney, E.E.; Hansen, T.H.; Suri, A.; Cemerski, S.; Allen, P.M.; Shaw, A.S. IL-12 enhances CTL synapse formation and induces self-reactivity. J. Immunol., 2009, 182, 1351-1361.
165. Tietze, J.K.; Wilkins, D.E.; Sckisel, G.D.; Bouchlaka, M.N.; Alderson, K.L.; Weiss, J.M.; Ames, E.; Bruhn, K.W.; Craft, N.; Wiltrout, R.H.; Longo, D.L.; Lanier, L.L.; Blazar, B.R.; Redelman, D.; Murphy, W.J. Delineation of antigen-specific and antigennonspecific CD8(+) memory T-cell responses after cytokine-based cancer immunotherapy. Blood, 2012, 119, 3073-3083.
166. Bacon, C.M.; Petricoin, E.F.; Ortaldo, J.R.; Rees, R.C.; Larner, A.C.; Johnston, J.A.; O’Shea, J.J. Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes. Proc. Natl. Acad. Sci. U.S.A., 1995, 92, 7307-7311.
167. Jacobson, N.G.; Szabo, S.J.; Weber-Nordt, R.M.; Zhong, Z.; Schreiber, R.D.; Darnell, J.E.Jr; Murphy, K.M. Interleukin 12 signaling in T helper type 1 (Th1) cells involves tyrosine phosphorylation of signal transducer and activator of transcription (Stat)3 and Stat4. J. Exp. Med., 1995, 181, 1755-1762.
168. Thierfelder, W.E., van Deursen, J,M.; Yamamoto, K.; Tripp, R.A.; Sarawar, S.R.; Carson, R.T.; Sangster, M.Y.; Vignali, D.; Doherty, P.C.; Grosveld, G.C. Ihle J.N. Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells. Nature, 1996, 382, 171-174.
169. Schroeder, A.; Herrmann, A.; Cherryholmes, G.; Kowolik, C.; Buettner, R.; Pal, S.; Yu, H.; Müller-Newen, G.; Jove, R. Loss of androgen receptor expression promotes a stem-like cell phenotype in prostate cancer through STAT3 signaling. Cancer Res., 2014, 74, 1227-1237.