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

幽门螺杆菌CagA通过上调外泌体中的PD-L1水平促进胃癌的免疫逃逸

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作者: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

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.

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