{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T23:02:38Z","timestamp":1771801358714,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,8,16]],"date-time":"2012-08-16T00:00:00Z","timestamp":1345075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We characterized tumor microenvironment (<jats:styled-content style=\"fixed-case\">TME<\/jats:styled-content>) components of mobile tongue (<jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content>) cancer patients in terms of overall inflammatory infiltrate, focusing on the protumorigenic\/anti\u2010inflammatory phenotypes and on cancer\u2010associated fibroblasts (<jats:styled-content style=\"fixed-case\">CAF<\/jats:styled-content>s) in order to determine their interrelations and associations with clinical outcomes. In addition, by culturing tongue carcinoma cells (<jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\u20103) on a three\u2010dimensional myoma organotypic model that mimics <jats:styled-content style=\"fixed-case\">TME<\/jats:styled-content>, we attempted to investigate the possible existence of a molecular crosstalk between cancer cells and <jats:styled-content style=\"fixed-case\">TME<\/jats:styled-content> components. Analysis of 64 cases of <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content> cancer patients revealed that the overall density of the inflammatory infiltrate was inversely correlated to the density of <jats:styled-content style=\"fixed-case\">CAF<\/jats:styled-content>s (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.01), but that the cumulative density of the protumorigenic\/anti\u2010inflammatory phenotypes, including regulatory T cells (Tregs, Foxp3+), tumor\u2010associated macrophages (<jats:styled-content style=\"fixed-case\">TAM<\/jats:styled-content>2, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>163+), and potentially Tregs\u2010inducing immune cells (<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>80+), was directly correlated with the density of <jats:styled-content style=\"fixed-case\">CAF<\/jats:styled-content>s (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.01). The hazard ratio (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>) for recurrence in a <jats:styled-content style=\"fixed-case\">TME<\/jats:styled-content> rich in <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>163+ Foxp3+ <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>80+ was 2.9 (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.03\u20138.6, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.043 compared with low in <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>163+ Foxp3+ <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>80+). The <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content> for recurrence in a <jats:styled-content style=\"fixed-case\">TME<\/jats:styled-content> rich in <jats:styled-content style=\"fixed-case\">CAF<\/jats:styled-content>s was 4.1 (95% confidence interval [<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>] 1.3\u201312.8, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.012 compared with low in <jats:styled-content style=\"fixed-case\">CAF<\/jats:styled-content>s). In vitro studies showed cancer\u2010derived exosomes, epithelial\u2013mesenchymal transition process, fibroblast\u2010to\u2010<jats:styled-content style=\"fixed-case\">CAF<\/jats:styled-content>\u2010like cell transdifferentiation, and reciprocal interrelations between different cytokines suggesting the presence of molecular crosstalk between cancer cells and <jats:styled-content style=\"fixed-case\">TME<\/jats:styled-content> components. Collectively, these results highlighted the emerging need of new therapies targeting this crosstalk between the cancer cells and <jats:styled-content style=\"fixed-case\">TME<\/jats:styled-content> components in <jats:styled-content style=\"fixed-case\">MT<\/jats:styled-content> cancer.<\/jats:p>","DOI":"10.1002\/cam4.24","type":"journal-article","created":{"date-parts":[[2012,8,16]],"date-time":"2012-08-16T16:05:30Z","timestamp":1345133130000},"page":"128-140","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Molecular crosstalk between cancer cells and tumor microenvironment components suggests potential targets for new therapeutic approaches in mobile tongue cancer"],"prefix":"10.1002","volume":"1","author":[{"given":"Dan","family":"Dayan","sequence":"first","affiliation":[{"name":"The Maurice and Gabriela Goldschleger School of Dental Medicine Tel Aviv University Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuula","family":"Salo","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Oral Medicine, Institute of Dentistry University of Oulu Oulu Finland"},{"name":"Oulu University Hospital Oulu Finland"},{"name":"Institute of Dentistry University of Helsinki Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sirpa","family":"Salo","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Oral Medicine, Institute of Dentistry University of Oulu Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pia","family":"Nyberg","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Oral Medicine, Institute of Dentistry University of Oulu Oulu Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sini","family":"Nurmenniemi","sequence":"additional","affiliation":[{"name":"Department of 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