Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression

摘要: Failure of T cells to protect against cancer is thought result from lack antigen recognition, chronic activation, and/or suppression by other cells. Using a mouse sarcoma model, we show that glucose consumption tumors metabolically restricts cells, leading their dampened mTOR activity, glycolytic capacity, and IFN-γ production, thereby allowing tumor progression. We enhancing glycolysis in an antigenic "regressor" sufficient override the protective ability control growth. also checkpoint blockade antibodies CTLA-4, PD-1, PD-L1, which are used clinically, restore microenvironment, permitting cell production. Furthermore, found blocking PD-L1 directly on dampens inhibiting activity decreasing expression enzymes, reflecting role for utilization. Our results establish tumor-imposed metabolic restrictions can mediate hyporesponsiveness during cancer.