{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:26:56Z","timestamp":1789684016419,"version":"4.0.1"},"reference-count":45,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,11,29]],"date-time":"2020-11-29T00:00:00Z","timestamp":1606608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion and Science","award":["JSPS KAKENHI 19K09151 and 19K09180"],"award-info":[{"award-number":["JSPS KAKENHI 19K09151 and 19K09180"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colorectal cancer (CRC) cells often express Tn antigen, a tumor-associated truncated immature O-glycan (GalNAc\u03b1-O-Ser\/Thr) that can promote tumor progression. Immunotherapies against Tn antigen have been developed and are being evaluated in clinical trials. Tn antigen can also be considered a novel immune checkpoint that induces immunosuppressive signaling through glycan-biding lectins to lead effector T cell apoptosis. We evaluated the correlation of Tn antigen expression by immunohistochemistry with mismatch-repair (MMR) status, tumor-infiltrating lymphocytes, tumor cell PD-L1 expression, and clinicopathological characteristics in 507 CRC patients. Although 91.9% of CRCs showed negative or weak Tn antigen staining (Tn-negative\/weak), we identified a small subset of CRCs (8.1%) that displayed particularly intense and diffuse distribution of Tn antigen immunoreactivity (Tn-strong) that closely related to deficient MMR (dMMR). Moreover, 40 dMMR CRCs were stratified into 24 Tn-negative\/weak dMMR tumors (60.0%) exhibiting dense CD8+ lymphocyte infiltrate concomitant with a high rate of PD-L1 positivity, and 16 Tn-strong dMMR tumors (40.0%) that demonstrated CD8+ T cell exclusion and a lack of PD-L1 expression, which was comparable to those of proficient MMR. Our finding suggests that the immune cold subset of patients with Tn-strong dMMR CRC may be effectively treated with immune checkpoint blockade therapy or cellular immunotherapy targeting Tn antigen.<\/jats:p>","DOI":"10.3390\/ijms21239081","type":"journal-article","created":{"date-parts":[[2020,11,29]],"date-time":"2020-11-29T21:00:57Z","timestamp":1606683657000},"page":"9081","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Tn Antigen Expression Defines an Immune Cold Subset of Mismatch-Repair Deficient Colorectal Cancer"],"prefix":"10.3390","volume":"21","author":[{"given":"Takuro","family":"Matsumoto","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0966-4746","authenticated-orcid":false,"given":"Hirokazu","family":"Okayama","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shotaro","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"},{"name":"Department of Medical Electrophysiology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuharu","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nakano","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eisei","family":"Endo","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Kase","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misato","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Yamauchi","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyuki","family":"Kanke","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Onozawa","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shotaro","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5072-3520","authenticated-orcid":false,"given":"Motonobu","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zenichiro","family":"Saze","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Momma","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosaku","family":"Mimura","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"},{"name":"Department of Blood Transfusion and Transplantation Immunology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Kono","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nature11252","article-title":"Comprehensive molecular characterization of human colon and rectal cancer","volume":"487","author":"Network","year":"2012","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41571-019-0241-1","article-title":"Biomarker-guided therapy for colorectal cancer: Strength in complexity","volume":"17","author":"Sveen","year":"2020","journal-title":"Nat. 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