Diacylglycerol Kinase ζ Limits Cytokine-dependent Expansion of CD8⁺ T Cells with Broad Antitumor Capacity.

ABSTRACT: Interleukin-2 and -15 drive expansion/differentiation of cytotoxic CD8⁺ T cells that eliminate targets via antigen-independent killing. This property is clinically relevant for the improvement of T cell-based antitumor therapies. Diacylglycerol kinase α and ζ (DGKα/ζ) metabolize the diacylglycerol generated following antigen recognition by T lymphocytes. Enhanced expression of these two lipid kinases in tumor-infiltrating CD8⁺ T cells promotes a hyporesponsive state that contributes to tumor immune escape. Inhibition of these two enzymes might thus be of interest for potentiating conventional antigen-directed tumor elimination. In this study, we sought to characterize the contribution of DGKα and ζ to antigen-independent cytotoxic functions of CD8⁺ T cells.

SUBMITTER: Andrada E 

PROVIDER: S-EPMC5440620 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature