SITC 2021 | The metabolic manipulation of T-cells and tumor cells with fenofibrate to treat melanoma

Hildegund Ertl, MD, The Wistar Institute, Philadelphia, PA, explains how metabolic manipulations in pre-clinical animal models improve the efficacy of T-cell immunotherapy for treating melanoma. It has been observe that T-cells invading melanoma in mice become exhausted due to a lack of glucose and oxygen. Via treatment with the peroxisome proliferator-activated receptor (PPAR)-alpha transcription factor, fenofibrate, T-cells can be manipulated to use fatty acids prior to transferring them into the tumor. Dr. Ertl describes how the metabolic reprogramming of T-cells with fenofibrate improves the function of T-cells, ultimately leading to increased tumor regression. In contrast, directly treating a mouse with fenofibrate, as opposed to treating the T-cells, manipulates the tumor cells to use fatty acids. This causes the tumor cells to use less glucose, generating an increased amount of glucose for the T-cells, thereby improving T-cell function and tumor regression. This interview took place during the 36th Society for Immunotherapy of Cancer (SITC) Annual Meeting in Washington, D.C.