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

Abstract

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.

Figure 1. Mitochondria-mediated metabolic support in memory T cell anti-tumor immunity

The metabolic stresses in the tumor microenvironment, including nutrient deprivation, hypoxia, acidic environment and immunosuppressive cytokine milieu, suppress anti-tumor responses and metabolic fitness in effector T cells. These microenviornmental barriers could affect mitochondrial mass and activity that lead to impaired TCA cycle and changes in bioenergetic programm. However, memory T cells might maintain their anti-tumor immunity by resisting to these microenvironmental barriers or sustaining their mitochondrial mass and functions.