Glucose restriction on immune cells by cancer

Glucose restriction on immune cells by cancer

The researchers found that T cells that have stem cell-like properties are tied to longer survival and high tumor killing capacity in human cancer. Aerobic glycolysis regulates T cell function. However, whether and how primary cancer alters T cell glycolytic metabolism and affects tumor immunity in cancer patients remains a question.

Researchers report in the journal Nature Immunology that ovarian cancers imposed glucose restriction on T cells and dampened their function via maintaining high expression of microRNAs miR-101 and miR-26a, which constrained expression of the methyltransferase EZH2. 

EZH2 activated the Notch pathway by suppressing Notch repressors, stimulated T cell polyfunctional cytokine expression and promoted their survival via Bcl-2 signaling.

Moreover, small hairpin RNA–mediated knockdown of human EZH2 in T cells elicited poor antitumor immunity.

Together, these data unveil a metabolic target and mechanism of cancer immune evasion.