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Johnson, Douglas B; Estrada, Monica V; Salgado, Roberto; Sanchez, Violeta; Doxie, Deon B; Opalenik, Susan R; Vilgelm, Anna E; Feld, Emily; Johnson, Adam S; Greenplate, Allison R; Sanders, Melinda E; Lovly, Christine M; Frederick, Dennie T; Kelley, Mark C; Richmond, Ann; Irish, Jonathan M; Shyr, Yu; Sullivan, Ryan J; Puzanov, Igor; Sosman, Jeffrey A; Balko, Justin M
Nature communications, 01/2016, Letnik: 7, Številka: 1Journal Article
Anti-PD-1 therapy yields objective clinical responses in 30-40% of advanced melanoma patients. Since most patients do not respond, predictive biomarkers to guide treatment selection are needed. We hypothesize that MHC-I/II expression is required for tumour antigen presentation and may predict anti-PD-1 therapy response. In this study, across 60 melanoma cell lines, we find bimodal expression patterns of MHC-II, while MHC-I expression was ubiquitous. A unique subset of melanomas are capable of expressing MHC-II under basal or IFNγ-stimulated conditions. Using pathway analysis, we show that MHC-II(+) cell lines demonstrate signatures of 'PD-1 signalling', 'allograft rejection' and 'T-cell receptor signalling', among others. In two independent cohorts of anti-PD-1-treated melanoma patients, MHC-II positivity on tumour cells is associated with therapeutic response, progression-free and overall survival, as well as CD4(+) and CD8(+) tumour infiltrate. MHC-II(+) tumours can be identified by melanoma-specific immunohistochemistry using commercially available antibodies for HLA-DR to improve anti-PD-1 patient selection.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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