Psoriasis is a chronic inflammatory dermatitis, affecting approximately 2% of the population. Major clinical features include red, scaly patches on scalp, elbows, and knees, with or without severe arthritis. Several putative susceptibility loci have been mapped by parametric and non-parametric linkage analysis to chromosome regions 2p, 4q, 6p, 8q, 16q, 17q, and 20p; however, the most significant results and confirmation of linkage are only available for the 17q and 6p chromosome regions at present. In this study, 22 multiplex Italian families were investigated for linkage to 6p and 17q susceptibility regions, using a set of four microsatellites. These analyses failed to detect significant linkage with any of the examined markers. A genome-wide scan was then performed on one of the largest pedigrees, searching for an additional susceptibility locus. This study disclosed a putative linkage to chromosome 1cen-q21 markers. When these microsatellites were analyzed in the remaining families of the sample, a significant linkage was observed using both parametric and non-parametric methods. The highest two-point lod score value was obtained with D1S305 marker (3.75 at 0 = 0.05). Non-parametric analysis at this locus also demonstrated a significant excess of allele sharing (p = 0.0001).

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The identification of reliable and quantitative melanoma biomarkers may help an early diagnosis and may directly affect melanoma mortality and morbidity. The aim of the present study was to identify effective biomarkers by investigating the expression of 27 cytokines/chemokines in melanoma compared to healthy controls, both in serum and in tissue samples. Serum samples were from 232 patients recruited at the IDI-IRCCS hospital. Expression was quantified by xMAP technology, on 27 cytokines/chemokines, compared to the control sera. RNA expression data of the same 27 molecules were obtained from 511 melanoma- and healthy-tissue samples, from the GENT2 database. Statistical analysis involved a 3-step approach: analysis of the single-molecules by Mann–Whitney analysis; analysis of paired-molecules by Pearson correlation; and profile analysis by the machine learning algorithm Support Vector Machine (SVM). Single-molecule analysis of serum expression identified IL-1b, IL-6, IP-10, PDGF-BB, and RANTES differently expressed in melanoma (p < 0.05). Expression of IL-8, GM-CSF, MCP-1, and TNF-α was found to be significantly correlated with Breslow thickness. Eotaxin and MCP-1 were found differentially expressed in male vs. female patients. Tissue expression analysis identified very effective marker/predictor genes, namely, IL-1Ra, IL-7, MIP-1a, and MIP-1b, with individual AUC values of 0.88, 0.86, 0.93, 0.87, respectively. SVM analysis of the tissue expression data identified the combination of these four molecules as the most effective signature to discriminate melanoma patients (AUC = 0.98). Validation, using the GEPIA2 database on an additional 1019 independent samples, fully confirmed these observations. The present study demonstrates, for the first time, that the IL-1Ra, IL-7, MIP-1a, and MIP-1b gene signature discriminates melanoma from control tissues with extremely high efficacy. We therefore propose this 4-molecule combination as an effective melanoma marker.

Table of contentsMELANOMA BRIDGE 2015KEYNOTE SPEAKER PRESENTATIONSMolecular and immuno-advancesK1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanomaVashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A. DaviesK2 Non-mutational adaptive changes in melanoma cells exposed to BRAF and MEK inhibitors help the establishment of drug resistanceGennaro Ciliberto, Luigi Fattore, Debora Malpicci, Luigi Aurisicchio, Paolo Antonio Ascierto, Carlo M. Croce, Rita ManciniK3 Tumor-intrinsic beta-catenin signaling mediates tumor-immune avoidanceStefani Spranger, Thomas F. GajewskiK4 Intracellular tumor antigens as a source of targets of antibody-based immunotherapy of melanomaYangyang Wang, Soldano FerroneCombination therapiesK5 Harnessing radiotherapy to improve responses to immunotherapy in cancerClaire Vanpouille-Box, Erik Wennerberg, Karsten A. Pilones, Silvia C. Formenti, Sandra DemariaK6 Creating a T cell-inflamed tumor microenvironment overcomes resistance to checkpoint blockadeHaidong Tang, Yang Wang, Yang-Xin FuK7 Biomarkers for treatment decisions?Reinhard DummerK8 Combining oncolytic therapies in the era of checkpoint inhibitorsIgor PuzanovK9 Immune checkpoint blockade for melanoma: should we combine or sequence ipilimumab and PD-1 antibody therapy?Michael A. PostowNews in immunotherapyK10 An update on adjuvant and neoadjuvant therapy for melanomAhmad TarhiniK11 Targeting multiple inhibitory receptors in melanomaJoe-Marc Chauvin, Ornella Pagliano, Julien Fourcade, Zhaojun Sun, Hong Wang, Cindy Sanders, John M. Kirkwood, Tseng-hui Timothy Chen, Mark Maurer, Alan J. Korman, Hassane M. ZarourK12 Improving adoptive immune therapy using genetically engineered T cellsDavid F. StroncekTumor microenvironment and biomarkersK13 Myeloid cells and tumor exosomes: a crosstalk for assessing immunosuppression?Veronica Huber, Licia RivoltiniK14 Update on the SITC biomarker taskforce: progress and challengesMagdalena ThurinWorld-wide immunoscore task force: an updateK15 The immunoscore in colorectal cancer highlights the importance of digital scoring systems in surgical pathologyTilman Rau, Alessandro LugliK16 The immunoscore: toward an integrated immunomonitoring from the diagnosis to the follow up of cancer’s patientsFranck PagèsEconomic sustainability of melanoma treatments: regulatory, health technology assessment and market access issuesK17 Nivolumab, the regulatory experience in immunotherapyJorge Camarero, Arantxa SanchoK18 Evidence to optimize access for immunotherapiesClaudio JommiORAL PRESENTATIONSMolecular and immuno-advancesO1 Ipilimumab treatment results in CD4 T cell activation that is concomitant with a reduction in Tregs and MDSCsYago Pico de Coaña, Maria Wolodarski, Yuya Yoshimoto, Giusy Gentilcore, Isabel Poschke, Giuseppe V. Masucci, Johan Hansson, Rolf KiesslingO2 Evaluation of prognostic and therapeutic potential of COX-2 and PD-L1 in primary and metastatic melanomaGiosuè Scognamiglio, Francesco Sabbatino, Federica Zito Marino, Anna Maria Anniciello, Monica Cantile, Margherita Cerrone,...