Anti-tumor T cells- you are what you eat (#3)
Activated T cells engage aerobic glycolysis and anabolic metabolism for growth, proliferation, and effector functions. In contrast, resting memory CD8 T cells depend less on high rates of glycolysis and more on fatty acid oxidation to persist, self-renew and respond to secondary infection. This talk will discuss the concept of metabolic checkpoints for immune cells in tumors, referring to the idea that the nutrients utilized by different types of T cells can affect both their energetic demands and their functionality. In particular, the metabolic state of exhausted T cells found in tumors is only recently starting to be studied. Our data in mouse models of cancer suggest that a glucose-poor, fatty acid-rich tumor microenvironment limits aerobic glycolysis, but promotes fatty acid uptake in tumor-infiltrating T cells, which suppresses tumoricidal effector functions and increases PD-1 expression. This talk will discuss recent analyses of the signaling pathways that respond to these nutrient alterations in T cells in tumors and how this may relate to new modalities of treatment in combination with checkpoint blockade.