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

Douglas B. Johnson (), Monica V. Estrada, Roberto Salgado, Violeta Sanchez, Deon B. Doxie, Susan R. Opalenik, Anna E. Vilgelm, Emily Feld, Adam S. Johnson, Allison R. Greenplate, Melinda E. Sanders, Christine M. Lovly, Dennie T. Frederick, Mark C. Kelley, Ann Richmond, Jonathan M. Irish, Yu Shyr, Ryan J. Sullivan, Igor Puzanov, Jeffrey A. Sosman and Justin M. Balko ()
Additional contact information
Douglas B. Johnson: Vanderbilt University
Monica V. Estrada: Microbiology and Immunology, Vanderbilt University
Roberto Salgado: Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Boulevard de Waterloo 121
Violeta Sanchez: Microbiology and Immunology, Vanderbilt University
Deon B. Doxie: Vanderbilt University
Susan R. Opalenik: Vanderbilt University
Anna E. Vilgelm: Vanderbilt University
Emily Feld: Vanderbilt University
Adam S. Johnson: Microbiology and Immunology, Vanderbilt University
Allison R. Greenplate: Microbiology and Immunology, Vanderbilt University
Melinda E. Sanders: Microbiology and Immunology, Vanderbilt University
Christine M. Lovly: Vanderbilt University
Dennie T. Frederick: Massachusetts General Hospital
Mark C. Kelley: Vanderbilt University
Ann Richmond: Vanderbilt University
Jonathan M. Irish: Microbiology and Immunology, Vanderbilt University
Yu Shyr: Vanderbilt University
Ryan J. Sullivan: Tennessee Valley Healthcare System
Igor Puzanov: Vanderbilt University
Jeffrey A. Sosman: Vanderbilt University
Justin M. Balko: Vanderbilt University

Nature Communications, 2016, vol. 7, issue 1, 1-10

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/ncomms10582

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