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

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Science Immunology  25 Jan 2019:
Vol. 4, Issue 31, eaap9520
DOI: 10.1126/sciimmunol.aap9520

Rescuing T cell glycolysis

One reason T cells in the tumor microenvioronment (TME) become dysfunctional is that they compete with cancer cells for nutrients, particularly glucose. By studying the glucose metabolism of CD8+ T cells in the TME of mouse B16 and human melanomas, Gemta et al. report the activity of enzyme enolase 1 to be impaired. Enolase 1 catalyzes the synthesis of phosphenolpyruvate, which is dephosphorylated to generate pyruvate, the end product of glycolysis. In vitro, provision of pyruvate considerably improved the effector functions of CD8+ T cells isolated from murine melanomas. Pinning down enolase 1 as the rate-limiting step in glucose metabolism of tumor-infiltrating T cells begs the question whether targeting enolase 1 activity in these cells can be used to improve responsiveness to cancer immunotherapy.

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