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

Background: 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. Main content: 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. Conclusion: 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.