Apoptosis of tumor infiltrating effector TIM-3+CD8+T cells in colon cancer

作者：Kang Chiao Wen; Dutta Avijit; Chang Li Yuan; Mahalingam Jayashri; Lin Yung Chang; Chiang Jy Ming; Hsu Chen Yu; Huang Ching Tai; Su Wan Ting; Chu Yu Yi; Lin Chun Yen^*

来源：Scientific Reports, 2015, 5(1): 15659.

DOI：10.1038/srep15659

TIM-3 functions to enforce CD8+ T cell exhaustion, a dysfunctional state associated with the tolerization of tumor microenvironment. Here we report apoptosis of IFN-gamma competent TIM-3+ population of tumor-infiltrating CD8+ T cells in colon cancer. In humans suffering from colorectal cancer, TIM-3+ population is higher in cancer tissue-resident relative to peripheral blood CD8+ T cells. Both the TIM-3+ and TIM-3-cancer tissue-resident CD8+ T cells secrete IFN-gamma of comparable levels, although apoptotic cells are more in TIM-3+ compared to TIM-3-population. In mouse CT26 colon tumor model, majority of tumor-infiltrating CD8+ T cells express TIM-3 and execute cytolysis function with higher effector cytokine secretion and apoptosis in TIM-3+ compared to TIM-3- population. The tumor cells secrete galectin-9, which increases apoptosis of tumor-infiltrating CD8+ T cells. Galectin-9/TIM-3 signaling blockade with anti-TIM-3 antibody reduces the apoptosis and in addition, inhibits tumor growth in mice. The blockade increases therapeutic efficacy of cyclophosphamide to treat tumor in mice as well. These results reveal a previously unexplored role of TIM-3 on tumor-infiltrating CD8+ T cells in vivo.

• 出版日期2015-10-23
• 单位长春大学