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

J Invest Dermatol. 2021 Aug;141(8):1897-1905. doi: 10.1016/j.jid.2020.12.037. Epub 2021 Apr 13.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • 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

Substances

  • Antigens, Neoplasm
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Epitopes, T-Lymphocyte
  • Immune Checkpoint Inhibitors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor