The IL-17 axis in gastric carcinogenesis: From inflammation to oncogenic transformation

Gastric cancer (GC) remains a leading cause of global cancer mortality, with Helicobacter pylori (Hp)-induced chronic inflammation and immune dysregulation playing a central pathogenic role. This review consolidates current understanding of interleukin-17 (IL-17) in gastric oncogenesis, delineating its molecular mechanisms, Hp-driven inflammatory pathways, and emerging therapeutic implications. Moving beyond prior analyses of isolated IL-17 signaling components, we systematically evaluate its impact on tumor initiation, progression, metastasis, and therapy resistance. Produced primarily by Th17 cells, IL-17 amplifies Hp-triggered inflammation, accelerates tumor growth via NF-κB and STAT3 pathway activation, and promotes malignant transformation and angiogenesis through upregulation of matrix metalloproteinases (MMPs) and angiogenic factors. Furthermore, IL-17 remodels the tumor microenvironment (TME), fostering immunosuppression and therapeutic resistance. Paradoxically, IL-17 can also stimulate protective anti-tumor immunity, such as enhancing cytotoxic T-cell responses, suggesting context-dependent therapeutic potential. Epidemiological studies link specific IL-17 gene polymorphisms to increased GC susceptibility in Hp-infected individuals. While preclinical models and early clinical data indicate potential benefits of IL-17 pathway inhibition, careful management of associated immunosuppressive risks is essential. This review identifies IL-17 receptor C (IL-17RC) as a promising biomarker candidate for personalized strategies and underscores the therapeutic potential of targeting this axis. By integrating molecular pathogenesis with clinical insights, we clarify IL-17's dual roles in GC biology and propose a framework for biomarker-guided discovery and multimodal therapeutic approaches to improve outcomes in this aggressive malignancy.