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Currently, the immune compartment in relation to subtypes is poorly characterized. Here, we analyzed the immune compartment in bladder tumors and normal bladder urothelium with a focus on T cell subpopulations using flow cytometry and RNA sequencing. The results were investigated in relation to tumor invasiveness (NMIBC\/MIBC) and molecular subtypes according to the Lund Taxonomy system. Whereas the NMIBC\/MIBC differed in the overall immune infiltration only, the molecular subtypes differed both in terms of immune infiltration and immune compartment compositions. The Basal\/Squamous (Ba\/Sq) and genomically unstable (GU) tumors displayed increased immune infiltration compared to urothelial-like (Uro) tumors. Additionally, the GU tumors had a higher proportion of regulatory T cells within the immune compartment compared to Uro tumors. Furthermore, sequencing showed higher levels of exhaustion in CD8+ T cells from GU tumors compared to both Uro tumors and the control. Although no such difference was detected at the transcriptomic level in Uro tumors compared to the controls, CD8+ T cells in Uro tumors showed higher expression of several exhaustion markers at the protein level. Taken together, our findings indicate that depending on the molecular subtype, different immunotherapeutic interventions might be warranted.<\/jats:p>","DOI":"10.3390\/cells13110926","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T05:19:49Z","timestamp":1716873589000},"page":"926","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Distinct Infiltration of T Cell Populations in Bladder Cancer Molecular Subtypes"],"prefix":"10.3390","volume":"13","author":[{"given":"Viktor","family":"Sincic","sequence":"first","affiliation":[{"name":"Department of Immunotechnology, Lund University, 223 81 Lund, Sweden"},{"name":"CREATE Health Cancer Center, Lund University, 223 81 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken F.","family":"Arlenhold","sequence":"additional","affiliation":[{"name":"Department of Immunotechnology, Lund University, 223 81 Lund, Sweden"},{"name":"CREATE Health Cancer Center, Lund University, 223 81 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7368-8297","authenticated-orcid":false,"given":"Sarah","family":"Richtmann","sequence":"additional","affiliation":[{"name":"Department of Immunotechnology, Lund University, 223 81 Lund, Sweden"},{"name":"CREATE Health Cancer Center, Lund University, 223 81 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Lilljebj\u00f6rn","sequence":"additional","affiliation":[{"name":"Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, 221 84 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pontus","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Division of Oncology, Department of Clinical Sciences Lund, Lund University, 221 84 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7869-0473","authenticated-orcid":false,"given":"Gottfrid","family":"Sj\u00f6dahl","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Lund University, 205 02 Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mats","family":"Wokander","sequence":"additional","affiliation":[{"name":"Department of Urology, Sk\u00e5ne University Hospital, 205 02 Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"H\u00e4gerbrand","sequence":"additional","affiliation":[{"name":"Alligator Bioscience AB, Medicon Village, 223 63 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6687-1250","authenticated-orcid":false,"given":"Peter","family":"Ellmark","sequence":"additional","affiliation":[{"name":"Department of Immunotechnology, Lund University, 223 81 Lund, Sweden"},{"name":"Alligator Bioscience AB, Medicon Village, 223 63 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thoas","family":"Fioretos","sequence":"additional","affiliation":[{"name":"Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, 221 84 Lund, Sweden"},{"name":"Department of Clinical Genetics, University and Regional Laboratories Region Sk\u00e5ne, 221 85 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl A. 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