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

iScience (Dec 2023)

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

Affiliations

Jinfeng Wang: 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
Rilin Deng: Institute of Pathogen Biology and Immunology, College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082, Hunan, China
Shuai Chen: School of Integrated Traditional Chinese and Western Medicine, Hunan University of Traditional Chinese Medicine, Changsha 410208, Hunan, China
Shun Deng: 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
Qi Hu: Graduates School, University of South China, Hengyang 421001, Hunan, China
Biaoming Xu: Graduates School, University of South China, Hengyang 421001, Hunan, China
Junjun Li: Department of Pathology, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China
Zhuo He: 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
Mingjing Peng: 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
Sanlin Lei: Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
Tiexiang Ma: The Third Department of General Surgery, The Central Hospital of Xiangtan City, Xiangtan 411100, Hunan, China
Zhuo Chen: 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
Haizhen Zhu: Institute of Pathogen Biology and Immunology, College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082, Hunan, China
Chaohui Zuo: 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; School of Integrated Traditional Chinese and Western Medicine, Hunan University of Traditional Chinese Medicine, Changsha 410208, Hunan, China; Graduates School, University of South China, Hengyang 421001, Hunan, China; Corresponding author

Journal volume & issue: Vol. 26, no. 12
p. 108414

Abstract

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Summary: 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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