Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy

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-P...

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Vydáno v:	Nature communications Ročník 7; číslo 1; s. 10582 - 10
Hlavní autoři:	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.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 29.01.2016 Nature Publishing Group Nature Portfolio
Témata:	13/106 13/31 13/51 13/95 38/39 631/250/21/324 64/60 692/308 692/699/67/1059 692/699/67/1813/1634 82/51 Antibodies, Monoclonal - pharmacology Antibodies, Monoclonal, Humanized Cell Line, Tumor Gene Expression Regulation, Neoplastic - physiology Genes, MHC Class II - genetics Genotype Humanities and Social Sciences Humans Melanoma Melanoma - genetics Melanoma - metabolism multidisciplinary Nivolumab Programmed Cell Death 1 Receptor - antagonists & inhibitors RNA, Messenger - genetics RNA, Messenger - metabolism Science Science (multidisciplinary) Tumors
ISSN:	2041-1723, 2041-1723
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Shrnutí:	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. Immunotherapy is used to treat melanoma, however patient responses vary widely highlighting the need for factors that can predict therapeutic success. Here, the authors show that MHC-II molecules expressed by tumour cells are positively correlated with a good response to therapy and overall patient survival.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 content type line 14 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/ncomms10582