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

Jinfeng Wang; Rilin Deng; Shuai Chen; Shun Deng; Qi Hu; Biaoming Xu; Junjun Li; Zhuo He; Mingjing Peng; Sanlin Lei; Tiexiang Ma; Zhuo Chen; Haizhen Zhu; Chaohui Zuo

doi:10.1016/j.isci.2023.108414

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

iScience. 2023 Nov 9;26(12):108414. doi: 10.1016/j.isci.2023.108414. eCollection 2023 Dec 15.

Authors

Jinfeng Wang¹, Rilin Deng², Shuai Chen³, Shun Deng¹, Qi Hu⁴, Biaoming Xu⁴, Junjun Li⁵, Zhuo He¹, Mingjing Peng¹, Sanlin Lei⁶, Tiexiang Ma⁷, Zhuo Chen⁸, Haizhen Zhu², Chaohui Zuo^{1

3

4}

Affiliations

¹ Department of Gastroduodenal and Pancreatic Surgery, Translational Medicine Joint Research Center of Liver Cancer, Laboratory of Digestive Oncology, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Clinical Research Center For Tumor of Pancreaticobiliary Duodenal Junction In Hunan Province, Changsha 410013, Hunan, China.
² Institute of Pathogen Biology and Immunology, College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082, Hunan, China.
³ School of Integrated Traditional Chinese and Western Medicine, Hunan University of Traditional Chinese Medicine, Changsha 410208, Hunan, China.
⁴ Graduates School, University of South China, Hengyang 421001, Hunan, China.
⁵ Department of Pathology, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China.
⁶ Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China.
⁷ The Third Department of General Surgery, The Central Hospital of Xiangtan City, Xiangtan 411100, Hunan, China.
⁸ Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha 410082, Hunan, China.

Abstract

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.

Keywords: Cancer; Gastroenterology; Microbiology.