Research progress on the impact and mechanisms of helicobacter pylori infection on the efficacy of immunotherapy for gastric cancer

TL;DR

This paper reviews how Helicobacter pylori infection affects the effectiveness of immunotherapy for gastric cancer and explores the underlying mechanisms.

Contribution

The paper systematically summarizes the complex role of H. pylori in gastric cancer immunotherapy and suggests future research directions.

Findings

H. pylori influences gastric cancer development through virulence factors like CagA and VacA.

H. pylori may both hinder and enhance immunotherapy outcomes via PD-L1 upregulation and immune cell modulation.

Combining microbiome strategies with immunotherapy could improve treatment personalization.

Abstract

Helicobacter pylori (H. pylori), recognized as a Group I carcinogen by the World Health Organization, is a key etiological agent in gastric cancer (GC). The majority of GC patients, particularly in China, present at advanced stages with constrained therapeutic options. Tumor immunotherapy, especially immune checkpoint inhibitors targeting the PD-1/PD-L1 axis, has emerged as a promising strategy. However, immunotherapy benefits only a subset of patients. Notably, H. pylori infection plays a significant role in GC and may also influence the efficacy of immunotherapy.

This review systematically summarizes the role and mechanisms of H. pylori in GC development, progression, and immunotherapy, focusing on the following aspects. Pathogenic mechanisms: H. pylori drives GC development through virulence factors (e.g., CagA, VacA, urease), which induce chronic inflammation, epithelial damage, immune evasion, and remodeling of the tumor microenvironment. Impact on immunotherapy and underlying mechanisms: The clinical efficacy is conflicting, some studies associate H. pylori infection with poor prognosis following immunotherapy, while others to better responses. Proposed mechanisms include PD-L1 upregulation via multiple signaling pathways, modulation of immune cells within the tumor microenvironment, and gut microbiota alterations affecting PD-1/PD-L1 inhibitor efficacy.

H. pylori has a complex influence on GC immunotherapy. Further research is needed to clarify the underlying mechanisms and assess the predictive value of H. pylori testing in clinical practice. Combining microbiome-based strategies with immunotherapy may enable more personalized and effective treatment.