Impaired enolase 1 glycolytic activity restrains effector functions of tumor-infiltrating CD8⁺ T cells.

ABSTRACT: In the context of solid tumors, there is a positive correlation between the accumulation of cytotoxic CD8⁺ tumor-infiltrating lymphocytes (TILs) and favorable clinical outcomes. However, CD8⁺ TILs often exhibit a state of functional exhaustion, limiting their activity, and the underlying molecular basis of this dysfunction is not fully understood. Here, we show that TILs found in human and murine CD8⁺ melanomas are metabolically compromised with deficits in both glycolytic and oxidative metabolism. Although several studies have shown that tumors can outcompete T cells for glucose, thus limiting T cell metabolic activity, we report that a down-regulation in the activity of ENOLASE 1, a critical enzyme in the glycolytic pathway, represses glycolytic activity

SUBMITTER: Gemta LF 

PROVIDER: S-EPMC6824424 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature