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

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...

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Bibliographic Details
Published in:Journal of investigative dermatology 2021-08, Vol.141 (8), p.1897-1905
Main Authors: Lahman, Miranda C., Paulson, Kelly G., Nghiem, Paul T., Chapuis, Aude G.
Format: Article
Language:English
Subjects:
Adaptive Immunity
Antigens, Neoplasm - analysis
Antigens, Neoplasm - immunology
B7-H1 Antigen - antagonists & inhibitors
B7-H1 Antigen - metabolism
Biomarkers, Tumor - analysis
Biomarkers, Tumor - immunology
Carcinoma, Merkel Cell - diagnosis
Carcinoma, Merkel Cell - immunology
Carcinoma, Merkel Cell - therapy
Carcinoma, Merkel Cell - virology
Drug Resistance, Neoplasm
Epitopes, T-Lymphocyte - immunology
Humans
Immune Checkpoint Inhibitors - pharmacology
Immune Checkpoint Inhibitors - therapeutic use
Immunotherapy - methods
Lymphocytes, Tumor-Infiltrating - immunology
Merkel cell polyomavirus - immunology
Polyomavirus Infections - diagnosis
Polyomavirus Infections - immunology
Polyomavirus Infections - therapy
Polyomavirus Infections - virology
Programmed Cell Death 1 Receptor - antagonists & inhibitors
Programmed Cell Death 1 Receptor - metabolism
Skin Neoplasms - diagnosis
Skin Neoplasms - immunology
Skin Neoplasms - therapy
Skin Neoplasms - virology
T-Lymphocytes - immunology
Tumor Microenvironment - immunology
Tumor Virus Infections - diagnosis
Tumor Virus Infections - immunology
Tumor Virus Infections - therapy
Tumor Virus Infections - virology
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Summary: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.
ISSN:0022-202X
1523-1747
DOI:10.1016/j.jid.2020.12.037