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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

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

ABSTRACT

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-γ 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-γ 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. More... »

PAGES

15659

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep15659

DOI

http://dx.doi.org/10.1038/srep15659

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1007119358

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26493689


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