Lipid Metabolism in Tumor-infiltrating T Cells: Mechanisms and Applications

As an essential part of adaptive immunity, T cells coordinate the immune responses against pathogens and cancer cells. Lipid metabolism has emerged as a key regulator for the activation, differentiation, and effector functions of T cells. Therefore, uncovering the molecular mechanisms by which lipid metabolism dictates T cell biology is of vital importance. The tumor microenvironment is a hostile milieu, i.e. often characterized by nutrient restriction. In this environment, various cells, such as T cells and cancer cells, reprogram their metabolism, including their lipid metabolism, to meet their energy and functional needs. Here, we review the participation of fatty acid and cholesterol metabolism homeostasis in orchestrating T cell biology. We demonstrate how the tumor microenvironment reshapes the lipid metabolism in T cells. Importantly, we highlight the current cancer therapeutic interventions that target fatty acid and cholesterol metabolism of T cells. By offering a holistic understanding of how lipid metabolic adaption by T cells facilitates their immunosurveillance in the tumor microenvironment, we believe this review and the future studies might inspire the next-generation immunotherapies.