Fatty acid metabolism inCD8+T cell memory: Challenging current concepts

Summary CD 8 + T cells are key members of the adaptive immune response against infections and cancer. As we discuss in this review, these cells can present diverse metabolic requirements, which have been intensely studied during the past few years. Our current understanding suggests that aerobic glycolysis is a hallmark of activated CD 8 + T cells, while naive and memory (T mem ) cells often rely on oxidative phosphorylation, and thus mitochondrial metabolism is a crucial determinant of CD 8 + T mem cell development. Moreover, it has been proposed that CD 8 + T mem cells have a specific requirement for the oxidation of long‐chain fatty acids ( LC ‐ FAO ), a process modulated in lymphocytes by the enzyme CPT 1A. However, this notion relies heavily on the metabolic analysis of in vitro cultures and on chemical inhibition of CPT 1A. Therefore, we introduce more recent studies using genetic models to demonstrate that CPT 1A‐mediated LC ‐ FAO is dispensable for the development of CD 8 + T cell memory and protective immunity, and question the use of chemical inhibitors to target this enzyme. We discuss insights obtained from those and other studies analyzing the metabolic characteristics of CD 8 + T mem cells, and emphasize how T cells exhibit flexibility in their choice of metabolic fuel.