文章基本信息

标题：Functional assessment of the cell-autonomous role of NADase CD38 in regulating CD8 + T cell exhaustion
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作者：Kaili Ma ; Lina Sun ; Mingjing Shen 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：5
页码：1-21
DOI：10.1016/j.isci.2022.104347
语种：English
出版社：Elsevier
摘要：SummaryExhausted 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 althoughCd38deficiency partially reverses NAD+degradation and T cell dysfunctionin 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 andCd38−/−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.Graphical abstractDisplay OmittedHighlights•CD38 is upregulated on CD8+T cells by persistent antigen stimulation•Deletion of CD38 partially reverses NAD+degradation and T cell dysfunctionin vitro•CD38 deficiency fails to prevent or delay CD8+T cell exhaustion within tumor•NAD+levels in tumor infiltrated T cells are regulated by CD38 and other NADasesImmunology; Cell biology; Cancer