{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:59:04Z","timestamp":1792202344773,"version":"4.4.0"},"reference-count":32,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T00:00:00Z","timestamp":1649376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bayerisches Hochschulzentrum f\u00fcr China","award":["BayCHINA"],"award-info":[{"award-number":["BayCHINA"]}]},{"name":"German Federal Ministry of Education and Research","award":["01DO17022"],"award-info":[{"award-number":["01DO17022"]}]},{"name":"Capital\u2019s Funds for Health Improvement and Research","award":["CFH 2020-2-1026"],"award-info":[{"award-number":["CFH 2020-2-1026"]}]},{"name":"PKU-Baidu Fund","award":["2020BD034"],"award-info":[{"award-number":["2020BD034"]}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["CSC202006010387"],"award-info":[{"award-number":["CSC202006010387"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Helicobacter pylori infection induces a number of pro-inflammatory signaling pathways contributing to gastric inflammation and carcinogenesis and has been identified as a major risk factor for the development of gastric cancer (GC). Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling mediates immune regulatory processes, including tumor-driven immune escape. Programmed death ligand 1 (PD-L1) expressed on gastric epithelium can suppress the immune system by shutting down T cell effector function. In a human cohort of subjects with gastric lesions and GC analyzed by proteomics, STAT1 increased along the cascade of progression of precancerous gastric lesions to GC and was further associated with a poor prognosis of GC (Hazard Ratio (95% confidence interval): 2.34 (1.04\u20135.30)). We observed that STAT1 was activated in human H. pylori-positive gastritis, while in GC, STAT1, and its target gene, PD-L1, were significantly elevated. To confirm the dependency of H. pylori, we infected gastric epithelial cells in vitro and observed strong activation of STAT1 and upregulation of PD-L1, which depended on cytokines produced by immune cells. To investigate the correlation of immune infiltration with STAT1 activation and PD-L1 expression, we employed a mouse model of H. pylori-induced gastric lesions in an Rnf43-deficient background. Here, phosphorylated STAT1 and PD-L1 were correlated with immune infiltration and proliferation. STAT1 and PD-L1 were upregulated in gastric tumor tissues compared with normal tissues and were associated with immune infiltration and poor prognosis based on the TCGA-STAD database. H. pylori-induced activation of STAT1 and PD-L1 expression may prevent immune surveillance in the gastric mucosa, allowing premalignant lesions to progress to gastric cancer.<\/jats:p>","DOI":"10.3390\/ijms23084147","type":"journal-article","created":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T05:13:08Z","timestamp":1649481188000},"page":"4147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["JAK-STAT1 Signaling Pathway Is an Early Response to Helicobacter pylori Infection and Contributes to Immune Escape and Gastric Carcinogenesis"],"prefix":"10.3390","volume":"23","author":[{"given":"Xue","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing 100142, China"},{"name":"PYLOTUM Key Joint Laboratory for Upper GI Cancer, Peking University Cancer Hospital and Institute, Beijing 100142, China"},{"name":"Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaifeng","family":"Pan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing 100142, China"},{"name":"PYLOTUM Key Joint Laboratory for Upper GI Cancer, Peking University Cancer Hospital and Institute, Beijing 100142, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Vieth","sequence":"additional","affiliation":[{"name":"PYLOTUM Key Joint Laboratory for Upper GI Cancer, Peking University Cancer Hospital and Institute, Beijing 100142, China"},{"name":"Institute of Pathology, Friedrich-Alexander University Erlangen-Nuremberg, Klinikum Bayreuth, 95445 Bayreuth, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9110-3950","authenticated-orcid":false,"given":"Markus","family":"Gerhard","sequence":"additional","affiliation":[{"name":"PYLOTUM Key Joint Laboratory for Upper GI Cancer, Peking University Cancer Hospital and Institute, Beijing 100142, China"},{"name":"Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8336-5552","authenticated-orcid":false,"given":"Wenqing","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing 100142, China"},{"name":"PYLOTUM Key Joint Laboratory for Upper GI Cancer, Peking University Cancer Hospital and Institute, Beijing 100142, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4602-4927","authenticated-orcid":false,"given":"Raquel","family":"Mej\u00edas-Luque","sequence":"additional","affiliation":[{"name":"PYLOTUM Key Joint Laboratory for Upper GI Cancer, Peking University Cancer Hospital and Institute, Beijing 100142, China"},{"name":"Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1002\/(SICI)1097-0215(19991126)83:5<615::AID-IJC8>3.0.CO;2-L","article-title":"Evolution of precancerous lesions in a rural Chinese population at high risk of gastric cancer","volume":"83","author":"You","year":"1999","journal-title":"Int. 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