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A butter-borne abettor of immunotherapy

Chuan He, Ludwig Cancer Research Chicago
Chuan He

Researchers co-led by Ludwig Chicago’s Chuan He reported in a November paper in Nature that dietary trans-vaccenic acid (TVA), the predominant trans fatty acid in human milk, directly promotes effector CD8+ T cell function and anti-tumour immunity in animal models. Only about 12%-19% of TVA—which cannot be produced by humans and comes primarily from beef, lamb and dairy products—is converted into a derivative, indicating it has some other activity. Chuan and his colleagues homed in on it when they constructed a blood nutrient library totaling 255 compounds and screened them for their ability to activate CD8+ T cells. TVA came up tops. The researchers found that TVA inactivates the GPR43 receptor on T cells, which is activated by fatty acids produced by gut bacteria. GPR43 silencing switches on signaling through the cAMP–PKA–CREB axis, a cellular signaling pathway that drives T cell survival, differentiation and proliferation. Analysis of blood samples from lymphoma patients showed that those with higher levels of circulating TVA tend to respond better to CAR-T cell immunotherapy. Supplementation with dietary TVA suppressed tumor growth in mouse models of colon cancer and melanoma, and appeared to improve T cell infiltration of tumors. It also notably reduced metastasis in a spontaneous colon cancer model. These effects were lost in mice engineered to lack the GPR43 receptor. The findings suggest TVA could prove to be an effective dietary supplement to elevate human immunity against cancer and improve outcomes of cancer immunotherapy.

Trans-vaccenic acid reprograms CD8+ T cells and anti-tumour immunity
Nature, 2023 November 22

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