Browse > Article

Marked Expansion of CD11c+CD8+ T-Cells in Melanoma-bearing Mice Induced by Anti-4-1BB Monoclonal Antibody  

Ju, Seong-A (Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan)
Park, Sang-Min (Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan)
Lee, Sang-Chul (Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan)
Kwon, Byoung S. (Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan)
Kim, Byung-Sam (Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan)
Publication Information
Molecules and Cells / v.24, no.1, 2007 , pp. 132-138 More about this Journal
Abstract
4-1BB (CD137), a member of the tumor necrosis factor receptor superfamily, is expressed on activated T-cells, and 4-1BB signaling due to interaction with 4-1BB ligand or ligation with anti-4-1BB monoclonal antibody (mAb) costimulates T cells. It has been shown that administration of anti-4-1BB mAb induces anti-tumor immunity in mice, but the nature of the cellular subsets responsible for this immunity is uncertain. In this study we found that anti-4-1BB mAb administration to B16F10 melanoma-bearing mice induced marked expansion of $CD11c^+CD8^+$ T-cells in parallel with suppression of pulmonary tumors. The mAb-treated mice produced higher levels of $IFN-{\gamma}$ in their tumor tissues, spleen and lymph nodes than mice exposed to control antibody. When the $CD11c^+CD8^+$ T-cells were purified and re-stimulated in vitro, they produced high levels of the Th1 cytokines, $IFN-{\gamma}$ and IL-2, but low levels of the Th2 cytokines, IL-4 and IL-10. Furthermore, they expressed high levels of 4-1BB and CD107a, a marker of activated cytotoxic T-lymphocytes. Our results suggest that $CD11c^+CD8^+$ T-cells play a role in the anti-tumor immunity induced by anti-4-1BB mAb.
Keywords
4-1BB; Anti-tummor immunity; Melanoma; Th1 cytokines;
Citations & Related Records

Times Cited By Web Of Science : 6  (Related Records In Web of Science)
연도 인용수 순위
  • Reference
1 Alleva, D. G.., Burger, C. J., and Elgert, K. D. (1994) Tumorinduced regulation of suppressor macrophage nitric oxid and TNF-alpha production. Role of tumor-derived IL-10, TGFbeta, and prostaglandin E2. J. Immunol. 153, 1674−1686
2 Kobayashi, M., Kobayashi, H., Pollard, R. B., and Suzuki, F. (1998) A pathogenic role of Th2 cells and their cytokine products on the pulmonary metastasis of murine B16 melanoma. J. Immunol. 160, 5869-5873
3 Maeda, H. and Shiraishi, A. (1996) TGF-beta contributes to the shift toward Th2-type responses through direct and IL-10-mediated pathways in tumor-bearing mice. J. Immunol. 156, 73-78
4 Seo, S. K., Choi, J. H., Kim, Y. H., Kang, W. J., Park, H. Y., et al. (2004) 4-1BB-mediated immunotherapy of rheumatoid arthritis. Nat. Med. 10, 1088-1094
5 Vinay, D. S. and Kwon, B.S. (1998) Role of 4-1BB in immune responses. Semin. Immunol. 10, 481-489
6 Park, E. K., Soh, B. Y., Jang, Y. S., Park, J. H., and Chung, G. H. (2001) Immune induction and modulation in mice following immunization with DNA encoding F protein of respiratory syncytial virus. Mol. Cells 12, 50-56
7 McAdam, A. J., Pulaski, B. A., Harkins, S. S., Hutter, E. K., Lord, E. M., et al. (1995) Synergistic effects of co-expression of the Th1-cytokines IL-2 and IFN-gamma on generation of murine tumor-reactive cytotoxic cells. Int. J. Cancer. 61, 628-634   DOI   ScienceOn
8 Yu, P., lee, Y., Liu, W., Krausz, T., Chong, A., et al. (2005) Intratumor depletion of $CD4^{+}$ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. JEM 201, 779-791   DOI   ScienceOn
9 Jang, Y. J., Nam, S. Y., Kim, M. S., Seong, R. H., Park, Y. S., et al. (2002) Simultaneous expression of allogenic class II MHC and B7.1 (CD80) molecules in A20 B-lymphoma cell line enhances tumor immunogenicity. Mol. Cells 13, 130-136
10 Li, Q., Carr, A., Ito, F., Teitz-Tennenbaum, S., and Chang, A. E. (2003) Polarization effects of 4-1BB during CD28 costimulation in generating tumor-reactive T cells for cancer immunotherapy. Cancer Res. 63, 2546-2552
11 Taraban, V. Y., Rowley, T. F., O'Brien, L., Chan, H. T., Haswell, L. E., et al. (2002) Expression and costimulatory effects of the TNF receptor superfamily members CD134 (OX40) and CD137 (4-1BB), and their role in the generation of anti-tumor immune responses. Eur. J. Immunol. 32, 3617-3627   DOI   ScienceOn
12 Melero, I., Shuford, W. W., Newby, S. A., Aruffo, A., Ledbetter, J. A., et al. (1997) Monoclonal antibodies against the 4-1BB T-cell activation molecule can eradicate established tumors. Nat. Med. 3, 682-685   DOI   ScienceOn
13 Boon, T., De Plaen, E., Lurquin, C., Van den Eynde, B., and van der Bruggen, P. (1992) Identification of tumor rejection antigens recognized by T lymphocytes. Cancer Surv. 13, 23-37
14 Kim, Y. H., Seo, S. K., Choi, B. K., Kang, W. J., Kim, C. H., et al. (2005) 4-1BB costimulation enhances HSV-1-specific $CD8^{+}$ T cell responses by the induction of $CD11c^{+}CD8^{+}$ T cells. Cell. Immunol. 238, 76-86
15 Pulendran, B., Lingappa, J., Kennedy, M. K., Smith, J., Teepe, M., et al. (1997) Developmental pathways of dendritic cells in vivo: distinct function, phenotype, and localization of dendritic cell subsets in FLT3 ligand-treated mice. J. Immunol. 159, 2222-2231
16 Weber, J. S. and Rosenberg, S. A. (1998) Modulation of murine tumor major histocompatibility antigens by cytokines in vivo and in vitro. Cancer Res. 48, 5818-5824
17 Betts, M. R., Brenchley, J. M., Price, D. A., De Rosa, S. C., Douek, D. C., et al. (2003) Sensitive and viable identification of antigen-specific CD8+ T cells by a flow cytometric assay for degranulation. J. Immunol. Methods 281, 65-78   DOI
18 Jang, I. K., Lee, Z. H., Kim, H. H., Hill, J. M., Kim J. D., et al. (2001) A Novel leucine-rich repeat protein (LRR-1): Potential involvement in 4-1BB-mediated signal transduction. Mol. Cells 12, 304-312
19 Chang, S. K., Park, B., Shin, J., Ahn, J. H., Kim, I. H., et al. (2002) Proto-oncogene PML enhances antigen presentation by MHC class I molecules in human lung cancer cells. Mol. Cells 14, 130-135
20 Ju, S. A., Lee, S. C., Kwon, T. H., Heo, S. K., Park, S. M., et al. (2005) Immunity to melanoma mediated by 4-1BB is associated with enhanced activity of tumour-infiltrating lymphocytes. Immunol. Cell Biol. 83, 344-351   DOI   ScienceOn
21 Huleatt, J. W. and Lefrancois, L. (1995) Antigen-driven induction of CD11c on intestinal intraepithelial lymphocytes and $CD8^{+}$ T cells in vivo. J. Immunol. 154, 5684-5693
22 Wilcox, R. A., Flies D. B., Zhu, G.., Johnson, A. J., Tamada, K., et al. (2002) Provision of antigen and CD137 signaling breaks immunological ignorance, promoting regression of poorly immunogenic tumors. J. Clin. Invest. 109, 651-659   DOI
23 Ghosh, P., Komschlies, K. L., Cippitelli, M., Longo, D. L., Subleski, J., et al. (1995) Gradual loss of T-helper 1 populations in spleens of mice during progressive tumor growth. J. Nat. Cancer Inst. 87, 1478-1483   DOI   ScienceOn
24 Miller, R. E., Jones, J., Le, T., Whitmore, J., Boiani, N., et al. (2002) 4-1BB-specific monoclonal antibody promotes the generation of tumor-specific immune responses by direct activation of CD8 T cells in a CD40-dependent manner. J. Immunol. 169, 1792-800
25 Kiertscher, S. M., Luo, J., Dubinett, S. M., and Roth, M. D. (2000) Tumors promote altered maturation and early apoptosis of monocyte-derived dendritic cells. J. Immunol. 164, 1269-1276   DOI