Single-cell dissection of prognostic architecture and immunotherap response in Helicobacter pylori infection-associated gastric cancer

PMCID: PMC12173458

PMID: 40525824

DOI: 10.7554/eLife.99337

Journal: eLife

Publication Date: 2025-6-17

Authors: Zhang X, Zhang G, Sang S, Fei Y, Cao X, et al.

Key Points

• H. pylori infection fundamentally reshapes gastric cancer's tumor microenvironment, increasing inflammatory and angiogenic cellular components
• iCAF abundance and angiogenic signatures could predict poor immunotherapy outcomes in gastric cancer patients
• Combination of immunotherapy with anti-angiogenic targeted therapy may represent a promising treatment strategy for H. pylori-associated gastric cancer

Summary

This single-cell transcriptome study comprehensively analyzed the tumor microenvironment (TME) in gastric cancer (GC) patients with varying Helicobacter pylori infection statuses. By examining 83,637 cells from 24 patients, researchers revealed critical molecular and cellular heterogeneity associated with H. pylori infection, demonstrating how bacterial presence dramatically influences cancer progression and immunotherapy potential.

The research uncovered significant TME alterations, particularly highlighting inflammatory and cancer-associated fibroblast (CAF) dynamics. Notably, H. pylori-associated GC exhibited increased inflammatory CAFs (iCAFs) and angiogenic tumor-associated macrophages, which were strongly correlated with suppressive immune responses. The study proposed that iCAFs interact with immune cells through pathways like NECTIN2-TIGIT, potentially mediating immune escape mechanisms that compromise immunotherapy efficacy.