Treatment with the PPARa agonist fenofibrate improves the efficacy of CD8⁺ T cell therapy for melanoma

Adoptive transfer of tumor antigen-specific CD8+ T cells can limit tumor progression but is hampered by the T cells' rapid functional impairment within the tumor microenvironment (TME). This is in part caused by metabolic stress due to lack of oxygen and glucose. Here, we report that fenofibrate treat-ment of human ex vivo expanded tumor-infiltrating lympho-cytes (TILs) improves their ability to limit melanoma progres-sion in a patient-derived xenograft (PDX) mouse model. TILs treated with fenofibrate, a peroxisome proliferator receptor alpha (PPARa) agonist, switch from glycolysis to fatty acid oxidation (FAO) and increase the ability to slow the progres-sion of autologous melanomas in mice with freshly trans-planted human tumor fragments or injected with tumor cell lines established from the patients' melanomas and ex vivo expanded TILs.