Tumor Cell-Intrinsic Decr2 Regulates Ferroptosis and Immunotherapy Efficacy.

ABSTRACT: Immune checkpoint blockade therapies have transformed the landscape of cancer care, but durable clinical responses are achieved in only a subset of patients. To identify genes that can contribute to immunotherapy resistance, a genome-wide CRISPR screen was performed. Selection for mutants that are resistant to T cell-mediated killing identified the gene encoding Decr2, a peroxisomal 2,4-dienoyl-CoA reductase. We show that Decr2 in tumor cells participates in CD8+ T cell-mediated tumor cell killing and that Decr2 knockdown reduces the efficacy of anti-PD-L1 therapy in vivo. Knocking down Decr2 expression resulted in diminished ferroptosis that was associated with reduced induction of polyunsaturated ether phospholipids. Analysis of tumor RNA sequencing data from patients with melanoma revea

SUBMITTER: Li S 

PROVIDER: S-EPMC12314507 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature