CD38-RyR2 axis-mediated signaling impedes CD8 T cell response to anti-PD1 therapy in cancer.

PD1 blockade therapy, harnessing the cytotoxic potential of CD8 T cells, has yielded clinical success in treating malignancies. However, its efficacy is often limited due to the progressive differentiation of intratumoral CD8 T cells into a hypofunctional state known as terminal exhaustion. Despite identifying CD8 T cell subsets associated with immunotherapy resistance, the molecular pathway triggering the resistance remains elusive.

Intracellular Acetyl CoA Potentiates the Therapeutic Efficacy of Antitumor CD8+ T Cells.

Unlabelled: Effector CD8+ T cells rely primarily on glucose metabolism to meet their biosynthetic and functional needs. However, nutritional limitations in the tumor microenvironment can cause T-cell hyporesponsiveness. Therefore, T cells must acquire metabolic traits enabling sustained effector function at the tumor site to elicit a robust antitumor immune response.