Role and mechanism of IL-33 in bacteria infection related gastric cancer continuum: From inflammation to tumor progression

Abstract

Gastric cancer, a globally prevalent malignant tumor, is characterized by low early diagnosis rate, high metastasis rate, and poor prognosis, particularly in East Asia, Eastern Europe, and South America. Helicobacter pylori (H. pylori) is recognized as the primary risk factor for gastric cancer. However, the fact that fewer than 3 % of infected individuals develop cancer suggests that other bacteria may also influence gastric carcinogenesis. A diverse community of microorganisms may interact with H. pylori, thereby driving disease progression. Here, the role of the cytokine IL-33, a member of the IL-1 family, is scrutinized. Its production can be induced by H. pylori through the activation of specific signaling pathways, and it contributes to the inflammatory environment by promoting the release of pro-inflammatory cytokines. This article reviews the conflicting evidence regarding IL-33's role in the progression from gastritis to gastric cancer and discusses the potential therapeutic implications of targeting the IL-33/ST2 axis, with various antibodies and inhibitors in development or undergoing clinical trials for inflammatory diseases. However, the role of IL-33 in gastric cancer treatment remains to be fully elucidated, with its effects potentially dependent on the cellular context and stage of cancer progression. In summary, this review provides a comprehensive overview of the intricate relationship between gastric microbiota, IL-33, and gastritis - gastric cancer transition, offering insights into potential therapeutic targets and the development of novel treatment strategies.