Helicobacter pylori CagA promotes immune evasion of gastric cancer by upregulating PD-L1 level in exosomes

被引：30

作者：

Wang, Jinfeng ^{[1
,2
]}

Deng, Rilin ^{[3
]}

Chen, Shuai ^{[4
]}

Deng, Shun ^{[1
,2
]}

Hu, Qi ^{[5
]}

Xu, Biaoming ^{[5
]}

Li, Junjun ^{[6
,7
]}

He, Zhuo ^{[1
,2
]}

Peng, Mingjing ^{[1
,2
]}

Lei, Sanlin ^{[8
]}

Ma, Tiexiang ^{[9
]}

Chen, Zhuo ^{[10
]}

Zhu, Haizhen ^{[3
]}

Zuo, Chaohui ^{[1
,2
,4
,5
]}

机构：

[1] Hunan Canc Hosp, Translat Med Joint Res Ctr Liver Canc, Dept Gastroduodenal & Pancreat Surg, Lab Digest Oncol, Changsha 410013, Hunan, Peoples R China

[2] Cent South Univ, Affiliated Canc Hosp, Clin Res Ctr Tumor Pancreaticobiliary Duodenal Jun, Xiangya Sch Med, Changsha 410013, Hunan, Peoples R China

[3] Hunan Univ, Inst Pathogen Biol & Immunol, Coll Biol, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Hunan, Peoples R China

[4] Hunan Univ Chinese Med, Sch Integrated Tradit Chinese & Western Med, Changsha 410208, Hunan, Peoples R China

[5] Univ South China, Grad Sch, Hengyang 421001, Hunan, Peoples R China

[6] Cent South Univ, Hunan Canc Hosp, Dept Pathol, Changsha 410013, Hunan, Peoples R China

[7] Cent South Univ, Affiliated Canc Hosp, Xiangya Sch Med, Changsha 410013, Hunan, Peoples R China

[8] Cent South Univ, Dept Gen Surg, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China

[9] Cent Hosp Xiangtan City, Dept Gen Surg 3, Xiangtan 411100, Hunan, Peoples R China

[10] Hunan Univ, Mol Sci & Biomed Lab MBL, State Key Lab Chemo Biosensing & Chemometr,Coll Bi, Coll Chem & Chem Engn,Aptamer Engn Ctr Hunan Prov, Changsha 410082, Hunan, Peoples R China

来源：

ISCIENCE | 2023年 / 26卷 / 12期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

TUMOR-SUPPRESSOR; EPITHELIAL-CELLS; T-CELLS; EXPRESSION; APOPTOSIS; PROTEIN; TARGET;

D O I：

10.1016/j.isci.2023.108414

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：

Cytotoxin-associated gene A (CagA) of Helicobacter pylori (Hp) may promote immune evasion of Hp -infected gastric cancer (GC), but potential mechanisms are still under explored. In this study, the positive rates of CagA and PD-L1 protein in tumor tissues and the high level of exosomal PD-L1 protein in plasma exosomes were significantly associated with the elevated stages of tumor node metastasis (TNM) in Hp infected GC. Moreover, the positive rate of CagA was positively correlated with the positive rate of PD-L1 in tumor tissues and the level of PD-L1 protein in plasma exosomes, and high level of exosomal PD-L1 might indicate poor prognosis of Hp-infected GC. Mechanically, CagA increased PD-L1 level in exosomes derived from GC cells by inhibiting p53 and miRNA-34a, suppressing proliferation and anticancer effect of CD8+ T cells. This study provides sights for understanding immune evasion mediated by PD-L1. Targeting CagA and exosomal PD-L1 may improve immunotherapy efficacy of Hp-infected GC.

引用

页数：17

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