Remarkable progress in cancer immunotherapy has revealed the power of harnessing immunity to combat cancer. However, the immunosuppressive nature of the tumor microenvironment remains a fundamental challenge to improving immune-based anti-cancer therapies. We aim to develop new immunotherapies by studying the nutrient utilization of immune cells in the tumors. Using an inducible Braf/Pten melanoma model, we found that tumors contain higher amounts of available free fatty acids (FFAs) and lower amounts of glucose than the blood. Exposure to high concentration of FFAs induced an exhaustion-like phenotype of CD8+ T cells. Furthermore, mice deficient of FFA transporter CD36 developed smaller tumors compared to wild-type control mice. Tumor-infiltrating Cd36-/- CD8+ T cells expressed lower level of inhibitory receptors, such as PD-1 and LAG-3. This study highlights an important role of lipid metabolism in regulating T cell exhaustion in the tumor microenvironment and reveals CD36 as a potential drug candidate for immunotherapy.
Citation Format: Guoliang Cui, Susan Kaech. Unsaturated fatty acids cause CD8+ T cell exhaustion in melanoma. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B063.
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