Targeting metabolic dysfunction of CD8 T cells and natural killer cells in cancer

Abstract

The importance of metabolic pathways in regulating immune responses is now well established, and a mapping of the bioenergetic metabolism of different immune cell types is under way. CD8 T cells and natural killer (NK) cells contribute to cancer immunosurveillance through their cytotoxic functions and secretion of cytokines and chemokines, complementing each other in target recognition mechanisms. Several immunotherapies leverage these cell types by either stimulating their activity or redirecting their specificity against tumour cells. However, the anticancer activity of CD8 T cells and NK cells is rapidly diminished in the tumour microenvironment, closely linked to a decline in their metabolic capacities. Various strategies have been developed to restore cancer immunosurveillance, including targeting bioenergetic metabolism or genetic engineering. This Review provides an overview of metabolic dysfunction in CD8 T cells and NK cells within the tumour microenvironment, highlighting current therapies aiming to overcome these issues. CD8 T cells and natural killer (NK) cells play a key role in cancer immunosurveillance. However, their anticancer activity is rapidly diminished in the tumour microenvironment, associated with a decline in their metabolic function. This Review provides an overview of metabolic programmes in CD8 T cells and NK cells, discusses the dysfunction that can occur in cancer, and assesses therapeutic strategies to overcome this.