Functional assessment of the cell-autonomous role of NADase CD38 in regulating CD8⁺ T cell exhaustion.

ABSTRACT: 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 tumo

SUBMITTER: Ma K 

PROVIDER: S-EPMC9117873 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature