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One hundred and ten formalin\u2010fixed paraffin\u2010embedded samples were collected from a retrospective cohort of 67 OTSCC patients and 10 non\u2010cancerous tongue samples. Targets including CD4, CD8, FOXP3, PD\u2010L1, and PD\u20101 were analyzed by immunohistochemistry. The Nanostring PanCancer Immune Profiling Panel was used for gene expression profiling. Data were externally validated in the The Cancer Genome Atlas (TCGA) head and neck (HNSCC), melanoma and lung squamous cell carcinoma (LSCC) cohorts. A 24\u2010immune gene signature was identified that discriminated more aggressive OTSCC cases, and although not prognostic in HNSCC was associated with survival in other TCGA cohorts (improved survival for melanoma, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001 and worse survival for LSCC, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.038). OTSCC exhibited concordant gene and immunohistochemical (IHC) features characterized by a TH\u20102 biased, proinflammatory profile with upregulated B cell and neutrophil gene activity and increased CD4, FOXP3, and PD\u2010L1 expression (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001 for all by IHC). Compared to less advanced disease, nodal involvement and recurrent OTSCC did not induce a different immune response although recurrent disease was characterized by significantly higher PD\u2010L1 expression (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.004 by SP263, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.013 by 22C3, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.004 for gene expression). Identification of a gene signature associated with different prognostic effects in other cancers highlights common pathways of immune dysregulation that are impacted by the tumor origin. The significant immunosuppressive signaling in OTSCC indicates primary failure of immune system to control carcinogenesis emphasizing the need for early, combination therapeutic approaches.<\/jats:p>","DOI":"10.1002\/cam4.3106","type":"journal-article","created":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T09:02:57Z","timestamp":1588928577000},"page":"4791-4807","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Characterization of the immune profile of oral tongue squamous cell carcinomas with advancing disease"],"prefix":"10.1002","volume":"9","author":[{"given":"Katie","family":"Meehan","sequence":"first","affiliation":[{"name":"Chinese University of Hong Kong  Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Connull","family":"Leslie","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology PathWest Laboratory Medicine Queen Elizabeth Medical Centre Nedlands WA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela","family":"Lucas","sequence":"additional","affiliation":[{"name":"University of Western Australia Crawley WA Australia"},{"name":"Department of Clinical Immunology PathWest and Sir Charles Gairdner Hospital Queen Elizabeth Medical Centre Nedlands WA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Jacques","sequence":"additional","affiliation":[{"name":"Institute for Health Research University of Notre Dame Fremantle WA Australia"},{"name":"Department of Research Sir Charles Gairdner Hospital Nedlands WA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bob","family":"Mirzai","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology PathWest Laboratory Medicine Queen Elizabeth Medical Centre Nedlands WA Australia"},{"name":"University of Western Australia Crawley WA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Lim","sequence":"additional","affiliation":[{"name":"Genomics WA Telethon Kids Institute West Perth WA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Bulsara","sequence":"additional","affiliation":[{"name":"Institute for Health Research University of Notre Dame Fremantle WA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasir","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Sir Charles Gairdner Hospital Nedlands WA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas C.","family":"Wong","sequence":"additional","affiliation":[{"name":"Monash Bioinformatics Platform Monash University Clayton VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Solomon","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre Melbourne VIC Australia"},{"name":"Department of Oncology Sir Peter MacCallum The University of Melbourne Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chady","family":"Sader","sequence":"additional","affiliation":[{"name":"University of Western Australia Crawley WA Australia"},{"name":"Department of Otolaryngology, Head and Neck Skull Base Surgery Sir Charles Gairdner Hospital Nedlands WA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Friedland","sequence":"additional","affiliation":[{"name":"University of Western Australia Crawley WA Australia"},{"name":"Department of Otolaryngology, Head and Neck Skull Base Surgery Sir Charles Gairdner Hospital Nedlands WA Australia"},{"name":"School of Medicine University of Notre Dame Fremantle WA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gisela","family":"Mir Arnau","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Semple","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0777-2279","authenticated-orcid":false,"given":"Annette M.","family":"Lim","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre Melbourne VIC Australia"},{"name":"Department of Oncology Sir Peter MacCallum The University of Melbourne Melbourne VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,5,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32591-7"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1602252"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2013.810716"},{"key":"e_1_2_11_5_1","first-page":"6501","article-title":"B7\u2013H1 blockade augments adoptive T\u2010cell immunotherapy for squamous cell carcinoma","volume":"63","author":"Strome SE","year":"2003","journal-title":"Cancer 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