Compartment-specific PPARδ activity controls the outcome of cancer-immune cell competition and immunotherapy efficacy.

Activating PPARδ in immune cells enhances tumor suppression and improves immunotherapy responses in mice with metastatic colorectal cancer.

• Why it matters: Most patients with solid tumors fail to sustain antitumor immunity due to immune cells being unable to outcompete cancer cells in the immunosuppressive tumor microenvironment, highlighting a need for strategies to boost immune cell function.
• What they did: The study examined PPARδ activity in cancer and immune cells, showing that its activation in cancer cells promotes growth, while activation in immune cells enhances CD8+ T cell fitness via chromatin remodeling and fatty acid oxidation, using pharmacological and genetic methods in mouse models and human CAR T cells.
• The result: Activating PPARδ in immune cells sensitizes resistant tumors to checkpoint blockade and improves immunotherapy outcomes, suggesting that compartment-specific PPARδ activity is a targetable driver of immune cell fitness for cancer treatment.