Immunoselection in vivo: independent loss of MHC class I and melanocyte differentiation antigen expression in metastatic melanoma

Int J Cancer. 1997 Apr 10;71(2):142-7. doi: 10.1002/(sici)1097-0215(19970410)71:2<142::aid-ijc3>;2-0.


Peptides derived from melanocyte differentiation antigens have been identified as targets for MHC class I-restricted cytolytic T lymphocytes (CTLs) in human melanoma Regression of antigen-expressing tumors as well as selection of antigen-loss variants in the presence of antigen-specific CTLs have previously been reported. In the present study, we determined the expression of the melanocyte differentiation antigens Melan A/MART-1 and tyrosinase by mRNA analysis and by immunohistochemical staining with the monoclonal antibodies (MAbs) A103 and T311. Co-expression of Melan A/MART-1 and tyrosinase was detected by both methods in 18/20 melanomas tested. However, immunohistochemistry provided additional information on intensity and microheterogeneity of antigen expression that cannot be detected by mRNA analysis as a molecular basis for the escape from CTL recognition of antigen-negative tumor cells. Comparative analysis of repeated biopsies of metastatic lesions in 5 HLA-A2+ patients showed a gradual loss of Melan A/MART-1 expression in 4/5 and of tyrosinase in 2/5 samples in association with tumor progression. However, 3 of these patients had growing antigen-positive tumors in the presence of antigen-specific CTLs. This led us to assess the expression of MHC class I, the essential restriction element for CTL recognition, and of HLA-A2. We found an unexpectedly high frequency of MHC class I-negative tumors (9/20). Loss of MHC class I expression was detected in 3/5 progressive tumors and isolated loss of HLA-A2 in 1/5 tumors. Our results suggest that strategies enhancing the expression of MHC class I and tumor-associated antigens need to be considered in attempts at making vaccination more effective.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / metabolism
  • Biopsy
  • DNA Primers / chemistry
  • Female
  • Genes, MHC Class I / physiology*
  • HLA-A2 Antigen / metabolism*
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / metabolism
  • Lymphatic Metastasis
  • MART-1 Antigen
  • Male
  • Melanoma / metabolism*
  • Middle Aged
  • Monophenol Monooxygenase / metabolism
  • Neoplasm Proteins / metabolism*
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Skin Neoplasms / metabolism


  • Antigens, Neoplasm
  • DNA Primers
  • HLA-A2 Antigen
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins
  • RNA, Messenger
  • Monophenol Monooxygenase