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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.


Our melanoma project is funded by the Department of Defense. We have a tent pending for the use of PPARa agonists to improve the efficacy of active immunotherapy of melanoma

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