{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T19:57:16Z","timestamp":1780775836054,"version":"3.54.1"},"reference-count":43,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science (JSPS)","award":["22H02912"],"award-info":[{"award-number":["22H02912"]}]},{"name":"Japan Society for the Promotion of Science (JSPS)","award":["22K08766"],"award-info":[{"award-number":["22K08766"]}]},{"name":"Japan Society for the Promotion of Science (JSPS)","award":["22K08792"],"award-info":[{"award-number":["22K08792"]}]},{"name":"Japan Society for the Promotion of Science (JSPS)","award":["21K08749"],"award-info":[{"award-number":["21K08749"]}]},{"name":"Japan Society for the Promotion of Science (JSPS)","award":["20K09098"],"award-info":[{"award-number":["20K09098"]}]},{"name":"Japan Society for the Promotion of Science (JSPS)","award":["19K07726"],"award-info":[{"award-number":["19K07726"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human leukocyte antigen class I (HLA-I) is considered a genetic pathogen for ulcerative colitis (UC). This study aimed to investigate the significance of DNA damage and HLA-I expression in infiltrating immune cells and immune checkpoint protein PD-L1 expression in dysplasia\/colitic cancer (CC) and sporadic colorectal cancer (SCRC). We performed immunohistochemical staining for HLA-I, PD-L1, \u03b3H2AX (DNA damage marker), and immune cell markers such as CD8, FOXP3, CD68, and CD163 (in surgically resected specimens from 17 SCRC patients with 12 adjacent normal mucosa (NM) and 9 UC patients with 18 dysplasia\/CC tumors. The ratio of membrane HLA-I-positive epithelial cells in UC and dysplasia\/CC tissues was significantly higher than that in NM and SCRC. High HLA-I expression in dysplasia\/CC was associated with high positivity of \u03b3H2AX and PD-L1 expression compared to SCRC. The infiltration of CD8-positive T cells and CD68-positive macrophages in HLA-I-high dysplasia\/CC was significantly higher than in UC and SCRC. Dysplasia\/CC specimens with DNA damage exhibited high levels of HLA-I-positive epithelial cells with high CD8- and CD68-positive immune cell infiltration compared to UC and SCRC specimens. Targeting DNA damage in UC may regulate immune cell infiltration, immune checkpoint proteins, and carcinogenesis by modulating DNA damage-induced HLA-I antigen presentation.<\/jats:p>","DOI":"10.3390\/ijms241713648","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T10:14:11Z","timestamp":1693822451000},"page":"13648","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["HLA Class I Expression Is Associated with DNA Damage and Immune Cell Infiltration into Dysplastic and Neoplastic Lesions in Ulcerative Colitis"],"prefix":"10.3390","volume":"24","author":[{"given":"Haruka","family":"Okami","sequence":"first","affiliation":[{"name":"Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Ozawa","sequence":"additional","affiliation":[{"name":"Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Sohda","sequence":"additional","affiliation":[{"name":"Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3284-4796","authenticated-orcid":false,"given":"Takehiko","family":"Yokobori","sequence":"additional","affiliation":[{"name":"Division of Integrated Oncology Research, Gunma University, Initiative for Advanced Research (GIAR), Maebashi 371-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuya","family":"Osone","sequence":"additional","affiliation":[{"name":"Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilguun","family":"Erkhem-Ochir","sequence":"additional","affiliation":[{"name":"Division of Integrated Oncology Research, Gunma University, Initiative for Advanced Research (GIAR), Maebashi 371-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gendensuren","family":"Dorjkhorloo","sequence":"additional","affiliation":[{"name":"Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3543-1874","authenticated-orcid":false,"given":"Takuya","family":"Shiraishi","sequence":"additional","affiliation":[{"name":"Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuhisa","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Sano","sequence":"additional","affiliation":[{"name":"Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Department of Surgery Japanese Red Cross Maebashi Hospital, Maebashi 371-0811, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroomi","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2287-7658","authenticated-orcid":false,"given":"Takashi","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, Graduate School of Medicine, Juntendo University, Bunkyo-ku 113-8431, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Oike","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8267-6917","authenticated-orcid":false,"given":"Hiro","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Shirabe","sequence":"additional","affiliation":[{"name":"Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Shibata","sequence":"additional","affiliation":[{"name":"Division of Molecular Oncological Pharmacy, Faculty of Pharmacy, Keio University, Minato-ku 108-8345, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Saeki","sequence":"additional","affiliation":[{"name":"Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/978-3-540-69297-3_21","article-title":"Aspirin and NSAIDs for the prevention of colorectal cancer","volume":"181","author":"Baron","year":"2009","journal-title":"Recent Results Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/978-3-642-30331-9_7","article-title":"Aspirin in prevention of sporadic colorectal cancer: Current clinical evidence and overall balance of risks and 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