BACKGROUND: Programmed cell death ligand 1 (PD-L1) is a cell surface molecule that plays a critical role in suppressing immune responses, mainly through binding of the PD-1 receptor on T lymphocytes. PD-L1 may be expressed by metastatic melanoma (MM). However, its clinical and biological significance remains unclear. Here, we investigated whether expression of PD-L1 in MM identifies a biologically more aggressive form of the disease, carrying prognostic relevance. PATIENTS AND METHODS: PD-L1 expression was analyzed by immunohistochemistry using two different antibodies in primary tumors and paired metastases from 81 melanoma patients treated at a single institution. Protein expression levels were correlated with PD-L1 mRNA, BRAF mutational status and clinical outcome. PD-L1(+) and PD-L1(-) subsets of the A375 cell line were stabilized in vitro and compared using gene expression profiling and functional assays. Results were confirmed using xenograft models. RESULTS: PD-L1 membrane positivity was detected in 30/81 (37%) of patients. By multivariate analysis, Breslow thickness and PD-L1 membrane positivity were independent risk factors for melanoma-specific death {PD-L1 5% cutoff [hazard ratio (HR) 3.92, confidence interval (CI) 95% 1.61-9.55 P < 0.003], PD-L1 as continuous variable (HR 1.03, 95% CI 1.02-1.04 P < 0.002)}. PD-L1 expression defined a subset of the

PD-L1 marks a subset of melanomas with a shorter overall survival and distinct genetic and morphological characteristics / Massi, D; Brusa, D; Merelli, B; Ciano, M; Audrito, V; Serra, S; Buonincontri, R; Baroni, G; Nassini, R; Minocci, D; Cattaneo, L; Tamborini, E; Carobbio, A; Rulli, E; Deaglio, S; Mandala, M. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - 25:12(2014), pp. 2433-2442. [10.1093/annonc/mdu452]

PD-L1 marks a subset of melanomas with a shorter overall survival and distinct genetic and morphological characteristics

Carobbio A;
2014

Abstract

BACKGROUND: Programmed cell death ligand 1 (PD-L1) is a cell surface molecule that plays a critical role in suppressing immune responses, mainly through binding of the PD-1 receptor on T lymphocytes. PD-L1 may be expressed by metastatic melanoma (MM). However, its clinical and biological significance remains unclear. Here, we investigated whether expression of PD-L1 in MM identifies a biologically more aggressive form of the disease, carrying prognostic relevance. PATIENTS AND METHODS: PD-L1 expression was analyzed by immunohistochemistry using two different antibodies in primary tumors and paired metastases from 81 melanoma patients treated at a single institution. Protein expression levels were correlated with PD-L1 mRNA, BRAF mutational status and clinical outcome. PD-L1(+) and PD-L1(-) subsets of the A375 cell line were stabilized in vitro and compared using gene expression profiling and functional assays. Results were confirmed using xenograft models. RESULTS: PD-L1 membrane positivity was detected in 30/81 (37%) of patients. By multivariate analysis, Breslow thickness and PD-L1 membrane positivity were independent risk factors for melanoma-specific death {PD-L1 5% cutoff [hazard ratio (HR) 3.92, confidence interval (CI) 95% 1.61-9.55 P < 0.003], PD-L1 as continuous variable (HR 1.03, 95% CI 1.02-1.04 P < 0.002)}. PD-L1 expression defined a subset of the
2014
25
12
2433
2442
PD-L1 marks a subset of melanomas with a shorter overall survival and distinct genetic and morphological characteristics / Massi, D; Brusa, D; Merelli, B; Ciano, M; Audrito, V; Serra, S; Buonincontri, R; Baroni, G; Nassini, R; Minocci, D; Cattaneo, L; Tamborini, E; Carobbio, A; Rulli, E; Deaglio, S; Mandala, M. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - 25:12(2014), pp. 2433-2442. [10.1093/annonc/mdu452]
Massi, D; Brusa, D; Merelli, B; Ciano, M; Audrito, V; Serra, S; Buonincontri, R; Baroni, G; Nassini, R; Minocci, D; Cattaneo, L; Tamborini, E; Carobbio, A; Rulli, E; Deaglio, S; Mandala, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1331671
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