GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE345nnn/GSE345464/primaryOK200Transcriptomics Mus musculusHomo sapiens Genome binding/occupancy profiling by high throughput sequencingExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE345464GEOGSEfalseCompartment-specific PPARδ activity controls the outcome of cancer – immune cell competition and immunotherapy efficacyMost patients with solid tumors fail to sustain anti-tumor immunity, in part because immune cells cannot outcompete cancer cells inside the immunosuppressive tumor microenvironment. Here, we identify the lipid-sensing transcription factor PPARδ as a compartment-specific determinant of cancer-immune fitness balance and immunotherapy efficacy. Activating PPARδ in cancer cells promotes their growth and impairs anti-tumor immunity, whereas activating it in immune cells drives tumor suppression and overrides tumor-promoting effects of cancer-intrinsic activation.Mechanistically, PPARδ enhances CD8+ T cell fitness against cancer through effector-associated chromatin and remodeling and Cpt1a-mediated fatty acid oxidation, which is partly necessary but not sufficient.Therapeutically, PPARδ-activated CD8+ T cells sensitize immunotherapy resistant microsatellite stable (MSS) metastatic colorectal cancer to checkpoint blockade in mice, and pharmacologic or genetic PPARδ activation enhances human CAR-T cell function. These findings identify compartment-specific PPARδ activity as a targetable driver of immune cell fitness that can be harnessed to improve outcomes in immunotherapy-resistant tumors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us musculusHomo sapiens