Reenergizing T cell anti-tumor immunity by harnessing immunometabolic checkpoints and machineries

•Metabolic stress in tumors impairs T cell anti-tumor immunity.•Memory T cells could be optimal cell type to sustain metabolic fitness in tumors.•Skewing memory T cell formation is a promising strategy in adoptive cell therapy.•Mitochondrial metabolism may be critical to sustain T cell tumoricidal functions.

T cells patrol our bodies preventing pathogenic infections and malignant cell outgrowth. However, T cells must be properly controlled because aberrant or persistent T cell responses can damage tissues and contribute to autoimmune diseases and other chronic inflammatory diseases including metabolic syndrome. One regulatory mechanism utilized in immune cells is immunometabolic regulation, which ensures immune cells properly respond to systemic and peripheral metabolic cues. Recent work has suggested that deregulated metabolism in tumor cells creates a microenvironmental barrier for mounting effective anti-tumor immune responses. Here, we discuss how tumor cells evade immunosurveillance by modulating metabolic checkpoints in immune cells and discuss how memory T cells could provide effective anti-tumor responses by sustaining metabolic fitness and longevity.