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

被引：11

作者：

Ma, Kaili ^{[1
,2
]}

Sun, Lina ^{[3
,4
,5
,6
]}

Shen, Mingjing ^{[7
]}

Zhang, Xin ^{[1
,2
,8
]}

Xiao, Zhen ^{[1
,2
]}

Wang, Jiajia ^{[1
,2
,9
]}

Liu, Xiaowei ^{[1
,2
]}

Jiang, Kanqiu ^{[7
]}

Qin, F. Xiao-Feng ^{[1
,2
]}

Guo, Feng ^{[10
]}

Zhang, Baojun ^{[3
,4
,5
,6
]}

Zhang, Lianjun ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, Inst Syst Med, CAMS Key Lab Synthet Biol Regulatory Element, Beijing 100005, Peoples R China

[2] Suzhou Inst Syst Med, Suzhou 215123, Peoples R China

[3] Xi An Jiao Tong Univ, Sch Basic Med Sci, Dept Pathogen Microbiol & Immunol, Xian, Shaanxi, Peoples R China

[4] Xi An Jiao Tong Univ, Hlth Sci Ctr, Translat Med Inst, Inst Infect & Immun, Xian, Shaanxi, Peoples R China

[5] Xi An Jiao Tong Univ, Key Lab Environm & Genes Related Dis, Xian, Shaanxi, Peoples R China

[6] Xian Key Lab Immune Related Dis, Xian, Shaanxi, Peoples R China

[7] Soochow Univ, Affiliated Hosp 2, Dept Thorac & Cardiac Surg, Suzhou 215004, Peoples R China

[8] China Pharmaceut Univ, Inst Pharmaceut Sci, Nanjing 211198, Jiangsu, Peoples R China

[9] China Pharmaceut Univ, Sch Engn, Nanjing 211198, Jiangsu, Peoples R China

[10] Nanjing Med Univ, Affiliated Suzhou Hosp, Dept Oncol, Suzhou, Peoples R China

来源：

ISCIENCE | 2022年 / 25卷 / 05期

基金：

中国国家自然科学基金;

关键词：

NAD(+) METABOLISM; CANCER;

D O I：

10.1016/j.isci.2022.104347

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：20

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