{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T01:35:14Z","timestamp":1782783314798,"version":"3.54.5"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T00:00:00Z","timestamp":1563494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology CR"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Immune cells and cytolytic activity within the tumor microenvironment are being intensively studied. Through transcriptome profiling, immune cell enumeration using the xCell tool and cytolytic activity quantification according to granzyme A (<jats:italic>GZMA<\/jats:italic>) and perforin (<jats:italic>PRF1<\/jats:italic>) mRNA levels, we investigated immunoreactivity in tumor and\/or tumor\u2010free tongue tissue samples from 31 patients with squamous cell carcinoma of the oral tongue and 14 healthy individuals (control tongue tissues). We found significantly altered immune cell compositions (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and elevated cytolytic activity (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) in tumor compared to tumor\u2010free samples, and altered infiltration of a subset of immune cells (e.g. CD8<jats:sup>+<\/jats:sup> T cells, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) as well as increased cytolytic activity (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) in tumor\u2010free compared to control samples. Controlling for patient age at diagnosis and tumor stage, Cox regression analysis showed that high cytolytic activity in tumor\u2010free samples associated with improved disease\u2010free survival (hazard ratio=\u20094.20, 95% CI = 1.09\u201316.20, <jats:italic>p<\/jats:italic> = 0.037). However, the degree of cytolytic activity in tumor samples did not provide prognostic information. Taken together, our results show the presence of cancer\u2010related immune responses in clinically tumor\u2010free tongue in patients with squamous cell carcinoma of the oral tongue. Measuring cytolytic activity in tumor\u2010free tongue samples contralateral to tumor might thus be an effective approach to predict clinical outcome.<\/jats:p>","DOI":"10.1002\/cjp2.138","type":"journal-article","created":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T14:23:59Z","timestamp":1561472639000},"page":"240-247","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["High immune cytolytic activity in tumor\u2010free tongue tissue confers better prognosis in patients with squamous cell carcinoma of the oral tongue"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6574-3628","authenticated-orcid":false,"given":"Xiaolian","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Medical Biosciences\/Pathology Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Boldrup","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences\/Pathology Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J","family":"Coates","sequence":"additional","affiliation":[{"name":"Regional Centre for Applied Molecular Oncology (RECAMO), Masaryk Memorial Cancer Institute  Brno Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Fahraeus","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences\/Pathology Ume\u00e5 University  Ume\u00e5 Sweden"},{"name":"Regional Centre for Applied Molecular Oncology (RECAMO), Masaryk Memorial Cancer Institute  Brno Czech Republic"},{"name":"Institute of Molecular Genetics University Paris 7, St. Louis Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences\/Pathology Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torben","family":"Wilms","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences\/ENT Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Norberg\u2010Spaak","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences\/ENT Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Sgaramella","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences\/Pathology Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Nylander","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences\/Pathology Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0014-x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032414-112049"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.67"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.12.019"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.03.023"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3909"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4287"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30789-X"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-018-2150-z"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1349-1"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01027-z"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-0685"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3839"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.12.033"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2018.11"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2018.01.008"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.4103\/1477-3163.104007"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14129"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14288"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep32579"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2011.01107.x"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2015.207"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0184201"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq871"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-018-6506-6"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(195309)6:5<963::AID-CNCR2820060515>3.0.CO;2-Q"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2982"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.102"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2014.81"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI72589"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046575"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-11-437"}],"container-title":["The Journal of Pathology: Clinical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcjp2.138","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cjp2.138","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cjp2.138","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cjp2.138","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T12:59:05Z","timestamp":1760273945000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cjp2.138"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,19]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["10.1002\/cjp2.138"],"URL":"https:\/\/doi.org\/10.1002\/cjp2.138","archive":["Portico"],"relation":{},"ISSN":["2056-4538","2056-4538"],"issn-type":[{"value":"2056-4538","type":"print"},{"value":"2056-4538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,19]]},"assertion":[{"value":"2019-01-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}