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. SosmanJustin M. Balko

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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.

Original languageEnglish
Article number10582
JournalNature communications
Volume7
DOIs
Publication statusPublished - 2016 Jan 29

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Johnson, D. B., Estrada, M. V., Salgado, R., Sanchez, V., Doxie, D. B., Opalenik, S. R., Vilgelm, A. E., Feld, E., Johnson, A. S., Greenplate, A. R., Sanders, M. E., Lovly, C. M., Frederick, D. T., Kelley, M. C., Richmond, A., Irish, J. M., Shyr, Y., Sullivan, R. J., Puzanov, I., ... Balko, J. M. (2016). Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy. Nature communications, 7, [10582]. https://doi.org/10.1038/ncomms10582