期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：6
页码：1809-1814
DOI：10.1073/pnas.1417636112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThe multifunctional ability of CTLs is downregulated by interaction between immune-checkpoint molecules expressed on CTLs and their ligands expressed on cancer cells, referred to as immune exhaustion. The antibody-mediated, immune-checkpoint blockade turned out to a promising method for immunotherapy against advanced melanoma. Metformin, a drug prescribed for patients with type 2 diabetes, has been recognized to have anti-cancer effect. We found that CD8+ tumor infiltrating lymphocytes (TILs) is a target of metformin. CD8+ TILs inevitably undergo immune exhaustion, characterized by diminished production of multiple cytokines such as IL-2, TNF, and IFN{gamma
