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While immunotherapy is a front-line cancer treatment, unresolved chronic inflammation and toxicities from immunotherapy often limit its anti-tumor activity. Endogenous clearance or resolution of inflammation may overcome this global intrinsic limitation of immunotherapy. Here, we demonstrate that immune checkpoint inhibitors induce the expression of sEH, which degrades the anti-inflammatory and pro-resolving EpFAs in the tumor microenvironment. Dietary ω-3 PUFAs supplementation and/or pharmacologic inhibition of sEH enhances the efficacy of ICI in multiple murine cancer models. Our results implicate the stabilization of endogenous EpFAs as a promising new strategy in cancer therapy. Increasing endogenous anti-inflammatory and pro-resolving EpFAs via dietary supplementation and inhibition of sEH may be critically important as an adjuvant to conventional cancer therapies.

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This page is a summary of: Enhancing cancer immunotherapy via inhibition of soluble epoxide hydrolase, Proceedings of the National Academy of Sciences, February 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2314085121.
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