Helicobacter pylori infection negatively affects response of gastric cancer to immunotherapy

Abstract

Background Helicobacter pylori (H. pylori) is a known risk factor for gastric cancer, possibly via the PD-1/L1 pathway, and this infection may reduce the efficacy of immune checkpoint inhibitors (ICIs). This study explored the effects of H. pylori infection status on survival outcomes in patients with gastric cancer.

Methods This single-center, retrospective study included patients with gastric adenocarcinoma between June 1985 and August 2022. Patients with different histological subtypes were excluded. Primary variables of interest included H. pylori infection status and treatment with ICIs. Other clinical information included demographics, cancer histology, the presence of other cancers, and vital status.

Results A total of 2930 patients were included, of whom 206 (7.0%) received ICIs, 196 (6.7%) had prior H. pylori infection, and 1037 (35.4%) had a diffuse subtype. Diffuse cancer subtypes were associated with better survival (P<0.05) at 3 and 5 years compared to intestinal-type adenocarcinomas. Diffuse cancers demonstrated better survival outcomes than intestinal cancers at 10 years, but only among H. pylori-positive patients (P=0.013). H. pylori positivity was associated with worse survival at 3 years (P=0.041) among patients taking ICIs, but not in those not receiving ICIs (P=0.325).

Conclusions These findings suggest H. pylori infection may be an obstacle to successful immunotherapy, and may interact with cancer subtypes to differentially impact survival. Future studies are needed to validate the potential prognostic value of H. pylori positivity in gastric cancer.

Keywords Helicobacter pylori, immunotherapy, gastric cancer

Ann Gastroenterol 2025; 38 (3): 262-269