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Nat Commun. 2016 Jan 29;7:10582. doi: 10.1038/ncomms10582.

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

Author information

1
Department of Medicine, Vanderbilt University, Nashville, 37232 Tennessee, USA.
2
Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, 37232 Tennessee, USA.
3
Department of Pathology, Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Boulevard de Waterloo 121, Brussels 1000, Belgium.
4
Department of Cancer Biology, Vanderbilt University, Nashville, 37232 Tennessee, USA.
5
Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, 37232 Tennessee, USA.
6
Department of Medicine, Massachusetts General Hospital, Boston, 02114 Massachusetts, USA.
7
Department of Surgical Oncology, Vanderbilt University, Nashville, 37232 Tennessee, USA.
8
Department of Biostatistics, Vanderbilt University, Nashville, 37232 Tennessee, USA.

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.

PMID:
26822383
PMCID:
PMC4740184
DOI:
10.1038/ncomms10582
[Indexed for MEDLINE]
Free PMC Article

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