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Quality Is King: Fundamental Insights into Tumor Antigenicity from Virus-Associated Merkel Cell Carcinoma

  • Miranda C. Lahman
    Affiliations
    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA
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  • Kelly G. Paulson
    Affiliations
    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA

    Medical Oncology, Swedish Cancer Institute, Seattle, Washington, USA

    Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington, USA
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  • Author Footnotes
    5 These authors contributed equally to this work.
    Paul T. Nghiem
    Footnotes
    5 These authors contributed equally to this work.
    Affiliations
    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA
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  • Author Footnotes
    5 These authors contributed equally to this work.
    Aude G. Chapuis
    Correspondence
    Correspondence: Aude G. Chapuis, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, USA.
    Footnotes
    5 These authors contributed equally to this work.
    Affiliations
    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA
    Search for articles by this author
  • Author Footnotes
    5 These authors contributed equally to this work.
Published:April 13, 2021DOI:https://doi.org/10.1016/j.jid.2020.12.037
      Merkel cell carcinoma (MCC) is a rare skin malignancy that is a paradigm cancer for solid tumor immunotherapy. MCCs associated with Merkel cell polyomavirus (virus-positive MCC [VP-MCC]) or chronic UV exposure (virus-negative MCC [VN-MCC]) are anti–PD(L)1 responsive, despite VP-MCC’s low mutational burden. This suggests that antigen quality, not merely mutation quantity, dictates immunotherapy responsiveness, and cell-based therapies targeting optimal antigens may be effective. Despite VP-MCC’s antigenic homogeneity, diverse T-cell infiltration patterns are observed, implying microenvironment plasticity and multifactorial contributions to immune recognition. Moreover, VP-MCC exemplifies how antitumor adaptive immunity can provide tumor burden biomarkers for early detection and disease monitoring.

      Abbreviations:

      BCR (B-cell receptor), HIV-KS (HIV-associated Kaposi Sarcoma), ICB (Immune checkpoint blockade), LT-Ag (large-T antigen), MB (Megabase), MCC (Merkel cell carcinoma), MCPyV (Merkel cell polyomavirus), ORR (overall response rate), TCR-T (TCR-transduced T cell), TIL (tumor-infiltrating lymphocyte), TMB (tumor mutational burden), VN-MCC (virus-negative Merkel cell carcinoma), VP-H&N (virus-positive head and neck), VP-MCC (virus-positive Merkel cell carcinoma)
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