Helicobacter pylori promotes gastric cancer progression through the tumor microenvironment.

Gastric cancer (GC) is a leading type of cancer. Although immunotherapy has yielded important recent progress in the treatment of GC, the prognosis remains poor due to drug resistance and frequent recurrence and metastasis. There are multiple known risk factors for GC, and infection with Helicobacter pylori is one of the most significant. The mechanisms underlying the associations of H. pylori and GC remain unclear, but it is well known that infection can alter the tumor microenvironment (TME). The TME and the tumor itself constitute a complete ecosystem, and the TME plays critical roles in tumor progression, metastasis, and drug resistance. H. pylori infection can act synergistically with the TME to cause DNA damage and abnormal expression of multiple genes and activation of signaling pathways. It also modulates the host immune system in ways that enhance the proliferation and metastasis of tumor cells, promote epithelial-mesenchymal transition, inhibit apoptosis, and provide energy support for tumor growth. This review elaborates myriad ways that H. pylori infections promote the occurrence and progression of GC by influencing the TME, providing new directions for immunotherapy treatments for this important disease. KEY POINTS: • H. pylori infections cause DNA damage and affect the repair of the TME to DNA damage. • H. pylori infections regulate oncogenes or activate the oncogenic signaling pathways. • H. pylori infections modulate the immune system within the TME.