The Heat Is On: 20-HETE Instructs an Immunosuppressive Phenotype in Cancer-Associated Fibroblasts

Abstract

Immunotherapy of cancer is a burgeoning field of research since the realization that our immune system intrinsically has the capacity to restrict tumor occurrence and progression. Though strategies to maximize antitumor T-cell activation are well established, the efficacy of these therapies is limited by an insufficient knowledge of the intricate tumor microenvironment and its capacity to thwart antitumor immunity. Chen and colleagues now uncover a novel immunosuppressive pathway in non-small cell lung carcinoma. Overexpression of cytochrome P450F2 in cancer cells increases production of 20-hydroxyeicosatetraenoic acid, which instructs the expression of immunosuppressive molecules in cancer-associated fibroblasts by binding the GPR75 receptor and activating STAT3/c-Jun signaling. This work proposes several innovative therapeutic anchor points that may improve the efficacy of existing immunotherapies.