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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Bibliographic Details
Published in:Nature communications Vol. 7; no. 1; pp. 10582 - 10
Main Authors: 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.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 29.01.2016
Nature Publishing Group
Nature Portfolio
Subjects:
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13/31
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692/699/67/1059
692/699/67/1813/1634
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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
Online Access:Get full text
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Summary: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.
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ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms10582