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

Author

Listed:
  • 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
    Tennessee Valley Healthcare System)

  • Emily Feld

    (Vanderbilt University)

  • Adam S. Johnson

    (Microbiology and Immunology, Vanderbilt University)

  • Allison R. Greenplate

    (Microbiology and Immunology, Vanderbilt University
    Vanderbilt University)

  • Melinda E. Sanders

    (Microbiology and Immunology, Vanderbilt University)

  • Christine M. Lovly

    (Vanderbilt University
    Vanderbilt University)

  • Dennie T. Frederick

    (Massachusetts General Hospital)

  • Mark C. Kelley

    (Vanderbilt University)

  • Ann Richmond

    (Vanderbilt University
    Tennessee Valley Healthcare System)

  • Jonathan M. Irish

    (Microbiology and Immunology, Vanderbilt University
    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
    Vanderbilt University)

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.

Suggested Citation

  • 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. San, 2016. "Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10582
    DOI: 10.1038/ncomms10582
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    Cited by:

    1. Jianting Long & Xihe Chen & Mian He & Shudan Ou & Yunhe Zhao & Qingjia Yan & Minjun Ma & Jingyu Chen & Xuping Qin & Xiangjun Zhou & Junjun Chu & Yanyan Han, 2024. "HLA-class II restricted TCR targeting human papillomavirus type 18 E7 induces solid tumor remission in mice," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Su Yin Lim & Elena Shklovskaya & Jenny H. Lee & Bernadette Pedersen & Ashleigh Stewart & Zizhen Ming & Mal Irvine & Brindha Shivalingam & Robyn P. M. Saw & Alexander M. Menzies & Matteo S. Carlino & R, 2023. "The molecular and functional landscape of resistance to immune checkpoint blockade in melanoma," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Kuang Du & Shiyou Wei & Zhi Wei & Dennie T. Frederick & Benchun Miao & Tabea Moll & Tian Tian & Eric Sugarman & Dmitry I. Gabrilovich & Ryan J. Sullivan & Lunxu Liu & Keith T. Flaherty & Genevieve M. , 2021. "Pathway signatures derived from on-treatment tumor specimens predict response to anti-PD1 blockade in metastatic melanoma," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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