Tumor masses support naïve T cell infiltration, activation, and differentiation into effectors

Thompson., et al. 2010 J. Exp. Med.. 207: 1791-1804

Speaker：Fang-Hsin Chang (張芳馨)                          Time：14:00~15:00, Nov. 17 2010

Commentator：Dr. Huan-Yao Lei (黎煥耀博士)        Place：Room 601

Abstract：

        Intratumoral lymphocytes, especially CD8+ cytotoxic T cells, are important effectors to control tumor growth [1]. Tumor-draining lymph nodes are generally considered as the primary sites where antigen-presenting cells (APCs) present tumor antigens and activate tumor-specific naïve T cells [2]. However, litter is known whether naïve T cells can be activated within tumors in situ. To address this question, the authors used an animal model where ovalbumin (OVA)-expressing B16 melanoma cells are recognized by OT-I TCR transgenic T cells. After injection of naïve OT-I cells into the tumor-bearing mice, CD8+ OT-I cells were present in OVA-positive tumor masses, expressed activation markers and proliferated. Notably, activation and proliferation of the intratumoral OT-I cells occurred even when lymph nodes were absent or T cell egress from lymph nodes was blocked, indicating that the antigen-specific intratumoral T cells can be activated independently of lymph nodes. The authors further demonstrated that both tumor cells and intratumoral APCs contributed to the antigen presentation and T cell activation in situ. In addition, the tumor-infiltrating OT-I cells expressed interferon γ, CD107a, or granzyme B in vivo or after ex vivo stimulation, and exerted cytotoxic activity in vitro, indicating that the intratumorally-primed T cells differentiated into effectors. Therefore, this study provides evidence that tumor masses can be alternative sites for recruitment, activation and differentiation of effector T cells, even though tumor tissues are considered as an immunosuppressive microenvironment. It also raises a possibility that enhancing intratumoral T cell priming or boosting their effector functions in situ may of therapeutic value.

References：

1.         Pages, F., et al., Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene, 2010. 29(8): p. 1093-102.

2.         Hargadon, K.M., et al., Incomplete differentiation of antigen-specific CD8 T cells in tumor-draining lymph nodes. J. Immunol., 2006. 177(9): p. 6081-90.