Interplay between pathogen-mediated immune evasion and innate immune negative regulation in gastrointestinal tumors.

Persistent colonization by gastrointestinal pathogens is an important environmental factor contributing to the development and progression of gastric and colorectal cancer. Helicobacter pylori (H. pylori), Epstein-Barr virus (EBV), Fusobacterium nucleatum (F. nucleatum), enterotoxigenic Bacteroides fragilis (ETBF), and pks-positive Escherichia coli (E. coli) can induce chronic inflammation and reshape the tumor microenvironment via virulence factors, epithelial barrier disruption, DNA damage, and immune dysregulation. Conventional views have largely focused on the tumor-promoting effects of chronic inflammation; however, this view does not fully explain the coexsistence of persistent inflammation and immune evasion during chronic infection. In this review, we proposed that the key feature of pathogen-associated inflammation is not simply its intensity but rather the imbalance between sustained inflammatory stimulation and insufficient immune elimination. Rather than treating pathogen-mediated immune evasion, host-derived innate immune negative regulation, and adaptive immune checkpoint suppression as parallel mechanisms, this review examined how these functionally distinct layers converge in gastrointestinal tumors. Pathogen immune evasion allows persistent microbial stimulation, host negative-feedback pathways dampen PRR- and interferon (IFN)-associated signaling, and checkpoint-mediated suppression further impairs cytotoxic clearance. Together, these processes create a state in which sustained inflammation coexists with insufficient immune elimination. This state can impair antigen presentation, cytotoxic immune responses, and pathogen clearance, thereby promoting immune tolerance and tumor progression. Understanding this mechanism may offer a conceptual basis for pathogen control, innate immune reprogramming, and precision therapeutic intervention in gastrointestinal tumors.