Abstract

Summary Exhausted CD8 + T cells with limited effector functions and high expression of multiple co-inhibitory receptors are one of the main barriers hindering antitumor immunity. The NADase CD38 has received considerable attention as a biomarker of CD8 + T cell exhaustion, but it remains unclear whether the increased CD38 directly promotes T cell dysfunctionality. Here, we surprisingly found that although Cd38 deficiency partially reverses NAD + degradation and T cell dysfunction in vitro , the terminal exhausted differentiation of adoptively transferred CD8 +  T cells in tumor is not impacted by either deficiency or overexpression of CD38. Monitoring the dynamic NAD + levels shows that NAD + levels are comparable between tumor infiltrated WT and Cd38 −/− CD8 + T cells. Therefore, our results suggest that decreased NAD + are correlated with T cell dysfunction, but deficiency of CD38 is not enough for rescuing NAD + in tumor infiltrated CD8 + T cells and fails to increase the efficacy of antitumor T cell therapy.