{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:41:35Z","timestamp":1793727695259,"version":"4.6.1"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The concept that human leukocyte antigen-G (HLA-G) expression is specifically in various malignant lesions but absent in adjacent normal tissues has been well documented, and HLA-G is acknowledged as a novel immune checkpoint.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, HLA-G expression in 523 gastric cancer (GC) lesions and 283 case-matched peritumoral tissues (PTTs) was analyzed by immunohistochemistry. The clinical significance of HLA-G expression in GC lesions and case-matched PTTs was evaluated, and a specific HLA-G-positive subpopulation in PTTs was identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Data showed that HLA-G expression was significantly different between GC lesions (370\/523, 70.7%) and PTTs (238\/283, 84.1%; <jats:italic>p<\/jats:italic>&amp;lt;0.001). HLA-G in GC lesions was more frequently observed in older patients (76.2% vs. 65.3%, <jats:italic>p<\/jats:italic>=0.006), and HLA-G in PTTs was more commonly observed in female patients (92.0% vs. 80.5%, <jats:italic>p<\/jats:italic>=0.014). Survival analysis revealed that HLA-G expression in PTTs (overall survival: 42.0 months vs. 56.7 months, <jats:italic>p<\/jats:italic>=0.023), but not in GC lesions (52.1 months vs. 50.9 months, <jats:italic>p<\/jats:italic>=0.623), is significantly associated with poor prognosis. The fundic gland mucous neck cells were the only subpopulation that expressed HLA-G.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our findings, for the first time, suggest that fundic gland mucous neck cell HLA-G expression in PTTs is associated with GC progression.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1660054","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T05:32:11Z","timestamp":1760592731000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["HLA-G expression in peritumoral fundic gland mucous neck cells, but not in tumor lesions, related to poor survival in patients with gastric cancer"],"prefix":"10.3389","volume":"16","author":[{"given":"Xia","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu-Yue","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Gang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Hua","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aifen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2326636","article-title":"A class I antigen, HLA-G, expressed in human trophoblasts","volume":"248","author":"Kovats","year":"1990","journal-title":"Science"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2021.01.004","article-title":"HLA-G\/LILRBs: A cancer immunotherapy challenge","volume":"7","author":"Carosella","year":"2021","journal-title":"Trends Cancer"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2337\/db05-0731","article-title":"The class I HLA repertoire of pancreatic islets comprises the nonclassical class Ib antigen HLA-G","volume":"55","author":"Cirulli","year":"2006","journal-title":"Diabetes"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-0809","article-title":"Erythroblasts secrete the nonclassical HLA-G molecule from primitive to definitive hematopoiesis","volume":"104","author":"Menier","year":"2004","journal-title":"Blood"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.2.289","article-title":"Identification of a thymic epithelial cell subset sharing expression of the class Ib HLA-G molecule with fetal trophoblasts","volume":"186","author":"Crisa","year":"1997","journal-title":"J Exp Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.jri.2006.01.006","article-title":"Differential expression of human leukocyte antigen-G (HLA-G) messenger RNAs and proteins in normal human prostate and prostatic adenocarcinoma","volume":"71","author":"Langat","year":"2006","journal-title":"J Reprod Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.698677","article-title":"HLA-G\/ILTs targeted solid cancer immunotherapy: opportunities and challenges","volume":"12","author":"Lin","year":"2021","journal-title":"Front Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.826074","article-title":"Role of HLA-G in viral infections","volume":"13","author":"Jasinski-Bergner","year":"2022","journal-title":"Front Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.902093","article-title":"Biological characteristics of HLA-G and its role in solid organ transplantation","volume":"13","author":"Liu","year":"2022","journal-title":"Front Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.592010","article-title":"Roles of HLA-G in the maternal-fetal immune microenvironment","volume":"11","author":"Xu","year":"2020","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.8.4510","article-title":"HLA-G expression in melanoma: a way for tumor cells to escape from immunosurveillance","volume":"95","author":"Paul","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22158265","article-title":"Kuppen PJK. 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