{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T17:32:12Z","timestamp":1761327132673,"version":"build-2065373602"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010116","name":"Medicinska Underst\u00c3\u00b6dsf\u00c3\u00b6reningen Liv och H\u00c3\u00a4lsa","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010116","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004155","name":"Magnus Ehrnroothin S\u00c3\u00a4\u00c3\u00a4ti\u00c3\u00b6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004155","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    \u03b22-integrins are a family of adhesion proteins expressed in immune cells that play multiple roles in anti-tumor immunity. \u03b22-integrins regulate tumor infiltration of anti-tumorigenic immune cells such as cytotoxic CD8\u2009+\u2009T cells and NK cells. However, they also regulate the activity of myeloid cells, such as macrophages, which can have both anti- and pro-tumorigenic properties. The role of \u03b22-integrins in urothelial cancer remains poorly understood. Here, we have investigated the role of different \u03b22-integrins, and their cytoplasmic regulators, in urothelial cancer, by utilizing RNA expression data. We found that\n                    <jats:italic>ITGAL<\/jats:italic>\n                    (encoding for CD11a) and\n                    <jats:italic>FERMT3<\/jats:italic>\n                    (encoding for the integrin regulator kindlin-3) have a positive correlation with patient survival. EcoTyper analysis revealed increased infiltration of CD8\u2009+\u2009T cells and NK cells in\n                    <jats:italic>ITGAL<\/jats:italic>\n                    high samples, but\n                    <jats:italic>ITGAL<\/jats:italic>\n                    or\n                    <jats:italic>FERMT3<\/jats:italic>\n                    expression did not correlate with response to immunotherapy. In contrast,\n                    <jats:italic>ITGAM<\/jats:italic>\n                    and\n                    <jats:italic>ITGAX<\/jats:italic>\n                    (which encode for myeloid markers CD11b and CD11c) and\n                    <jats:italic>FLNA<\/jats:italic>\n                    (encoding for the integrin regulator filamin A) correlated with poor survival and reduced responsiveness to immunotherapy and critically regulate the tumor myeloid immune landscape (M1\/M2 macrophages, cDC1 dendritic cells). Therefore, \u03b22-integrins may be explored in the future as biomarkers to differentiate urothelial cancer patients with different immune landscapes, responding differently to therapy.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0326015","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T17:27:08Z","timestamp":1761326828000},"page":"e0326015","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b22-integrins as biomarkers in urothelial cancer"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5592-9365","authenticated-orcid":true,"given":"Marc","family":"Llort Asens","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imran","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0354-8763","authenticated-orcid":true,"given":"Susanna Carola","family":"Fagerholm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"issue":"3","key":"pone.0326015.ref001","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"H Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"issue":"20","key":"pone.0326015.ref002","doi-asserted-by":"crossref","first-page":"4485","DOI":"10.1002\/cncr.33067","article-title":"A randomized phase 2 trial of pembrolizumab versus pembrolizumab and 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