PMID- 33110100 OWN - NLM STAT- MEDLINE DCOM- 20210226 LR - 20210803 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 10 IP - 1 DP - 2020 Oct 27 TI - A role for the immune system in advanced laryngeal cancer. PG - 18327 LID - 10.1038/s41598-020-73747-0 [doi] LID - 18327 AB - To investigate the role of the altered activation of the immune system in the prognosis of patients affected by laryngeal squamous cell carcinoma (LSCC). We analyzed 56 patients with advanced LSCC divided into two groups according to their prognosis: the first group relapsed within 24 months after treatment, the second group had no evidence of disease at 2 years. The presence of stromal tumor infiltrating lymphocytes (TILs) at the tumor-host border was investigated. In 43 patients we evaluated the expression of 395 genes related to immune system activation through a next generation sequencing panel. Priority-LASSO models and clustering analyses were integrated with multivariate Cox proportional hazard modeling to identify independent genes associated with relapse and estimate hazard ratios in relation to gene expression and TILs. TILs and the expression of genes related with immune system activation (FCGR1A, IFNA17, FCRLA, NCR3, KREMEN1, CD14, CD3G, CD19, CD20 and CD79A) were significantly associated with prognostic factors or disease specific survival. In patients with lymph node metastases and advanced T stage (pT4), the expression of other genes was altered. Low TILs count was highly associated with relapse within 2 years (p < 0.001). Low TILs and altered expression of specific genes associated with tumor-immune systems interactions emerged as independent risk factors, associated to poor prognosis and relapse within 2 years in advanced LSCC. Evaluation of patients' immune profile could be useful for prognosis and future therapeutic approaches towards personalized therapy. FAU - Tagliabue, Marta AU - Tagliabue M AD - Division of Otolaryngology and Head and Neck Surgery, IEO, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141, Milan, Italy. marta.tagliabue@ieo.it. FAU - Maffini, Fausto AU - Maffini F AD - Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy. FAU - Fumagalli, Caterina AU - Fumagalli C AD - Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy. FAU - Gandini, Sara AU - Gandini S AD - Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy. FAU - Lepanto, Daniela AU - Lepanto D AD - Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy. FAU - Corso, Federica AU - Corso F AD - Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy. FAU - Cacciola, Salvatore AU - Cacciola S AD - Division of Otolaryngology and Head and Neck Surgery, IEO, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141, Milan, Italy. FAU - Ranghiero, Alberto AU - Ranghiero A AD - Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy. FAU - Rappa, Alessandra AU - Rappa A AD - Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy. FAU - Vacirca, Davide AU - Vacirca D AD - Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy. FAU - Cossu Rocca, Maria AU - Cossu Rocca M AD - Department of Medical Oncology, Urogenital and Head and Neck Tumors Medical Treatment, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy. FAU - Alterio, Daniela AU - Alterio D AD - Division of Radiotherapy, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy. FAU - Guerini Rocco, Elena AU - Guerini Rocco E AD - Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy. AD - Department of Oncology and Hemato-Oncology, School of Medicine, State University of Milan, Milan, Italy. FAU - Cattaneo, Augusto AU - Cattaneo A AD - Division of Otolaryngology and Head and Neck Surgery, IEO, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141, Milan, Italy. FAU - Chu, Francesco AU - Chu F AD - Division of Otolaryngology and Head and Neck Surgery, IEO, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141, Milan, Italy. FAU - Zorzi, Stefano AU - Zorzi S AD - Division of Otolaryngology and Head and Neck Surgery, IEO, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141, Milan, Italy. FAU - Curigliano, Giuseppe AU - Curigliano G AD - Department of Oncology and Hemato-Oncology, School of Medicine, State University of Milan, Milan, Italy. AD - Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy. FAU - Chiocca, Susanna AU - Chiocca S AD - Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139, Milan, Italy. FAU - Barberis, Massimo AU - Barberis M AD - Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy. FAU - Viale, Giuseppe AU - Viale G AD - Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy. AD - Department of Oncology and Hemato-Oncology, School of Medicine, State University of Milan, Milan, Italy. FAU - Ansarin, Mohssen AU - Ansarin M AD - Division of Otolaryngology and Head and Neck Surgery, IEO, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141, Milan, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201027 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 SB - IM EIN - Sci Rep. 2021 May 3;11(1):9760. PMID: 33941821 MH - Aged MH - Disease-Free Survival MH - Female MH - Gene Expression Regulation, Neoplastic/genetics MH - Humans MH - Immunity/genetics/immunology MH - Laryngeal Neoplasms/diagnosis/*immunology/pathology MH - Lymphocytes, Tumor-Infiltrating/immunology/pathology MH - Male MH - Middle Aged MH - Neoplasm Recurrence, Local/immunology/metabolism MH - Prognosis MH - Retrospective Studies MH - Sequence Analysis, RNA PMC - PMC7591515 COIS- The authors declare no competing interests. EDAT- 2020/10/29 06:00 MHDA- 2021/02/27 06:00 PMCR- 2020/10/27 CRDT- 2020/10/28 05:35 PHST- 2020/04/26 00:00 [received] PHST- 2020/09/17 00:00 [accepted] PHST- 2020/10/28 05:35 [entrez] PHST- 2020/10/29 06:00 [pubmed] PHST- 2021/02/27 06:00 [medline] PHST- 2020/10/27 00:00 [pmc-release] AID - 10.1038/s41598-020-73747-0 [pii] AID - 73747 [pii] AID - 10.1038/s41598-020-73747-0 [doi] PST - epublish SO - Sci Rep. 2020 Oct 27;10(1):18327. doi: 10.1038/s41598-020-73747-0.