CD8 agonism functionally activates memory T cells and enhances antitumor immunity

Abstract

Memory CD8⁺ T cells mature after antigen clearance and ultimately express CD8 protein at levels higher than those detected in effector CD8⁺ T cells. However, it is not clear whether engagement of CD8 in the absence of antigenic stimulation will result in the functional activation of T cells. Here, we found that CD8 antibody-mediated activation of memory CD8⁺ T cells triggered T cell receptor (TCR) downstream signaling, enhanced T cell-mediated cytotoxicity and promoted effector cytokine production in a glucose- and glutamine-dependent manner. Furthermore, pretreatment of memory CD8⁺ T cells with an agonistic anti-CD8 antibody enhanced their tumoricidal activity in vitro and in vivo. From these studies, we conclude that CD8 agonism activates glucose and glutamine metabolism in memory T cells and enhances the efficacy of memory T cell-based cancer immunotherapy.

Keywords: CD8+ T cells; TCR signaling; immunometabolism; immunotherapy; memory T cells.