Administration of Agonistic Anti-4-1BB Monoclonal Antibody Inhibits Melanoma Metastasis Via IFN-${\gamma}$ Production

  • Ju, Seong-A (Immunomodulation Research Center, University of Ulsan) ;
  • Lee, Sang-Chul (Immunomodulation Research Center, University of Ulsan) ;
  • Seok, Moon-Hong (Institute of Basic Sciences, Kyungpook National University) ;
  • Kim, Byung-Sam (Immunomodulation Research Center, University of Ulsan)
  • Published : 2004.06.01

Abstract

The purpose of this study was to analyze inhibitory effects of anti-4-1BB monoclonal antibody on melanoma metastasis The 4-1BB (CD137) T cell molecule is a member of the TNF receptor family and its activation by either 4-1BB ligand or antibody induces T cell activation and growth. In the present study, administration of anti-4-1BB mAb induced inhibition of melanoma metastasis. Agonistic anti-4-1BB mAb induced not only CD$8^+$4-1BBT cells but also CD$8^+$IFN-${\gamma}$$^{+}$ T cell population. In the presence of anti-CD3 antibody, lymphocytes produced high levels of IFN-${\gamma}$ and low levels of IL-4 in anti-4-1BB mAb treated group. Exposure of melanoma cells to IFN-${\gamma}$ induced expression of MHC-I molecules. Thus, the increase in number of CD$8^+$T cells and enhanced MHC-I expression on B16F10 cells by augmented IFN-${\gamma}$ production in response to anti-4-1BB mAb may result in suppression of tumor growth and metastasis.s.

Keywords

References

  1. Bellone M, Iezzi G, Manfredi AA, Protti MP, Dellabone P, Casorati G, and Rugarli C (1994) In vitro priming of cytotoxic T lymphocytes against poorly immunogenic epitopes by engineered antigen-presenting cells. Eur J Immunol 24: 2691-2698 https://doi.org/10.1002/eji.1830241118
  2. Bloom MB, Perry LD, Robbins PF, Li Y, EI-Gamil M, Rosenberg SA, and Yang JC (1997) Identification of tyrosinase-related protein 2 as a tumor rejection antigen for the B16 melanoma. J Exp Med 185: 453-460 https://doi.org/10.1084/jem.185.3.453
  3. Boehm U, Klamp T, Groot M, and Howard JC (1997) Cellular responses to $interferon-{\gamma}.$ Annu Rev Immunol 15: 749-795 https://doi.org/10.1146/annurev.immunol.15.1.749
  4. Boon T, De Plaen E, Lurquin C, Van den Eynde B, van der Bruggen P, Traversari C, Amar-Costesec A, and Van Pel A (1992) Identification of tumour rejection antigens recognized by T lymphocytes. Cancer Surv 13: 23-37
  5. Cannons JL, Choi Y, and Watts TH (2000) Role of TNF receptor-associated factor 2 and p38 mitogen-activated protein kinase activation during 4-1BB-dependent immune response. J Immunol 165: 6193-6204 https://doi.org/10.4049/jimmunol.165.11.6193
  6. Dighe AS, Richards L, and Schreiber RD (1994) Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative $IFN-{\gamma}$ receptors. Immunity 1: 447-456 https://doi.org/10.1016/1074-7613(94)90087-6
  7. Hamaoka T and Fujiwara H (1987) Phenotypically and functionally distinct T-cell subsets in anti-tumor responses. Immunol Today 8: 267-273 https://doi.org/10.1016/0167-5699(87)90187-3
  8. Harada M, Tamada K, Abe K, Li T, Onoe Y, Tada H, Tatsugami K, Ando T, Kimura G, and Nomoto K (1998) Characterization of B16 melanoma-specific cytotoxic T lymphocytes. Cancer Immunol Immunother 47:198-204 https://doi.org/10.1007/s002620050521
  9. Hurtado JC, Kim YJ, and Kwon BS (1997) Signals through 4-1BB are costimulatory to previously activated splenic T cells and inhibit activation-induced cell death. J Immunol 158: 2600-2609
  10. Kaplan, DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ, and Schreiber RD (1998) Demonstration of an interferon ${\gamma}-dependent$ tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci USA 95: 7556-7561 https://doi.org/10.1073/pnas.95.13.7556
  11. Kawano Y, Taniguchi K, Toshitani A, and Nomoto K (1986) Synergistic defense system by cooperative natural effetors against metastasis of B16 melanoma cells in H-2-associated control: different behavior of $H-2^+$ and $H-2^-$ cells in metastatic processes. J Immunol 136: 4729-4734
  12. Kim JA, Averbook BJ, Chambers K, Rothchild K, Kjaegaard J, Papay R, and Shu S (2001) Divergent effects of 4-1BB antibodies on antitumor immunity and on tumor-reactive T-cell generation. Cancer Res 61: 2031-2037
  13. Kwon BS and Weissman SM (1989) cDNA sequences of two inducible T cell genes. Proc Natl Acad Sci USA 86: 1963-1967 https://doi.org/10.1073/pnas.86.6.1963
  14. Li Y, Hellstrome KE, Newby SA, and Chen L (1996) Costimulation by CD48 and B7-1 induces immunity against pooly immunogenic tumors. J Exp Med 183: 639-644 https://doi.org/10.1084/jem.183.2.639
  15. Melero I, Johnston JV, Shuford WW, Mittler RS, and Chen L (1998) NK1.1 cells express 4-1BB (CDw137) costimulatory molecules and are required for tumor immunity elicited by anti-4-1BB monoclonal antibodies. Cell Immunol 190: 167-172 https://doi.org/10.1006/cimm.1998.1396
  16. Melero I, Shuford WW, Newby SA, Aruffo A, Ledbetter JA, Hellstrom KE, Mittler RS, and Chen L (1997) Monoclonal antibodies against the 4-1BB T-cell activation molecule can eradicate established tumors. Nat Med 3: 682-685 https://doi.org/10.1038/nm0697-682
  17. Mueller DL, Jenkins MK, and Schwarz RH (1989) Clonal expansion versus functional clonal inactivation: a costimulatory signaling pathway determines the outcome of T cell antigen receptor occupancy. Annu Rev Immunol 7: 445-480 https://doi.org/10.1146/annurev.iy.07.040189.002305
  18. Ryan A, Wilcox, Dallas BF, Gefeng Z, Aaron JJ, Tamada K, Andrei I, Scott ES, Larry RP, and Chen L (2002) Provision of antigen and CD137 signaling breaks immunological ignorance, promoting regression of poorly immunogrnic tumors. J Clin Invest 109: 651-659 https://doi.org/10.1172/JCI200214184
  19. Sica G and Chen L (2000) Modulation of the immune response through 4-1BB. Adv Exp Med Biol 465: 355-362 https://doi.org/10.1007/0-306-46817-4_30
  20. Takahashi C, Mittler RS, and Vella AT (1999) 4-1BB is a bona fide CD8 T cell survival signal. J Immunol 162: 5037-5040
  21. Vinay DS and Kwon BS (1998) Role of 4-1BB in immune regulation. Semin Immunol 10: 481-489 https://doi.org/10.1006/smim.1998.0157
  22. Webber JS and Rosenberg SA (1988) Modulation of murine tumor major histocompatibility antigens by cytokines in vivo and in vitro. Cancer Res 48: 5818-5824
  23. Wilcox RA and Chen L (2002) Immunotherapy of human papillomavirus-associated malignancies and the challenges posed by T-cell tolerance. Front Biosci 7: 853-871 https://doi.org/10.2741/wilcox
  24. Yokoyama T, Yoshie O, Aso H, Ebina T, and Ishida N (1986) Inhibition of intravascular mouse melanoma dissemination by recombinant human interferon ${\alpha}$ A/D. Jpn J Cancer Res 77: 80-84