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Approximately half of the world's population is infected with <jats:styled-content style=\"fixed-case\"><jats:italic>H. pylori<\/jats:italic><\/jats:styled-content>, making gastric cancer the fourth leading cause of cancer\u2010related deaths worldwide. Innate immunity significantly contributes to systemic and local immune responses, maintains homeostasis, and serves as the vital link to adaptive immunity, and in doing so, mediates <jats:styled-content style=\"fixed-case\"><jats:italic>H. pylori<\/jats:italic><\/jats:styled-content> infection outcomes and consequent cancer risk and development. The gastric innate immune system, composed of gastric epithelial and myeloid cells, is uniquely challenged by its need to interact simultaneously and precisely with commensal microbiota, exogenous pathogens, ingested substances, and endogenous exfoliated cells. Additionally, innate immunity can be detrimental by promoting chronic infection and fibrosis, creating an environment conducive to tumor development. This review summarizes and discusses the complex role of innate immunity in <jats:styled-content style=\"fixed-case\"><jats:italic>H. pylori<\/jats:italic><\/jats:styled-content> infection and subsequent gastric oncogenesis, and in doing so, provides insights into how these pathways can be exploited to improve prevention and treatment.<\/jats:p>","DOI":"10.1111\/hel.70015","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T03:08:31Z","timestamp":1742267311000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Innate Immunity in <i>Helicobacter pylori<\/i> Infection and Gastric Oncogenesis"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8949-2297","authenticated-orcid":false,"given":"Yuheng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Peking Union Medical College Hospital Chinese Academy of 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