title: microRNA Expression in Sentinel Nodes from Progressing Melanoma Patients Identifies Networks Associated with Dysfunctional Immune Response.
abstract: Sentinel node biopsy (SNB) is a main staging biomarker in melanoma and is the first lymph node to drain the tumor, thus representing the immunological site where anti-tumor immune dysfunction is established and where potential prognostic immune markers can be identified. Here we analyzed microRNA (miR) profiles in archival tumor-positive SNBs derived from melanoma patients with different outcomes and performed an integrated analysis of transcriptional data to identify deregulated immune signaling networks. Twenty-six miRs were differentially expressed in melanoma-positive SNB samples between patients with disease progression and non-progressing patients, the majority being previously reported in the regulation of immune responses. A significant variation in miR expression levels was confirmed in an independent set of SNB samples. Integrated information from genome-wide transcriptional profiles and in vitro assessment in immune cells led to the identification of miRs associated with the regulation of the TNF receptor superfamily member 8 (TNFRSF8) gene encoding the CD30 receptor, a marker increased in lymphocytes of melanoma patients with progressive disease. These findings indicate that miRs are involved in the regulation of pathways leading to immune dysfunction in the sentinel node and may provide valuable markers for developing prognostic molecular signatures for the identification of stage III melanoma patients at risk of recurrence.
authors.affiliation: Immunotherapy Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy. viviana.vallacchi@istitutotumori.mi.it.
authors.forename: Viviana
authors.initials: V
authors.lastname: Vallacchi
authors.affiliation: Immunotherapy Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy. chiara.camisaschi@istitutotumori.mi.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Camisaschi
authors.affiliation: Functional Genomics and Bioinformatics, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy. matteo.dugo@istitutotumori.mi.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Dugo
authors.affiliation: Immunotherapy Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy. elisabetta.vergani@istitutotumori.mi.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Vergani
authors.affiliation: Immunotherapy Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy. paola.deho@istitutotumori.mi.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Deho
authors.affiliation: Molecular Pathology Unit, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy. ambra.gualeni@istitutotumori.mi.it.
authors.forename: Ambra
authors.initials: A
authors.lastname: Gualeni
authors.affiliation: Immunotherapy Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy. veronica.huber@istitutotumori.mi.it.
authors.forename: Veronica
authors.initials: V
authors.lastname: Huber
authors.affiliation: Molecular Pathology Unit, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy. annunziata.gloghini@istitutotumori.mi.it.
authors.forename: Annunziata
authors.initials: A
authors.lastname: Gloghini
authors.affiliation: Melanoma and Sarcoma Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy. andrea.maurichi@istitutotumori.mi.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Maurichi
authors.affiliation: Melanoma and Sarcoma Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy. mario.santinami@istitutotumori.mi.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Santinami
authors.affiliation: Functional Genomics and Bioinformatics, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy. marialuisa.sensi@istitutotumori.mi.it.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Sensi
authors.affiliation: Immunotherapy Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy. chiara.castelli@istitutotumori.mi.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Castelli
authors.affiliation: Immunotherapy Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy. licia.rivoltini@istitutotumori.mi.it.
authors.forename: Licia
authors.initials: L
authors.lastname: Rivoltini
authors.affiliation: Immunotherapy Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy. monica.rodolfo@istitutotumori.mi.it.
authors.forename: Monica
authors.initials: M
authors.lastname: Rodolfo
keywords: CD30; immunosuppression; melanoma; microRNA; sentinel node biopsy