Melanoma antigen recognition by tumour-infiltrating T lymphocytes (TIL): Effect of differential expression of Melan-A/MART-1

T. Ramirez-Montagut, D. M. Andrews, A. Ihara, S. Pervaiz, F. Pandolfi, P. J. Van Den Elsen, R. Waitkus, L. A. Boyle, M. Hishii, J. T. Kurnick

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

We have isolated, from an individual patient with metastatic melanoma, a series of eight TIL clones capable of lysing autologous melanoma cell targets. Six of the eight clones expressed TCRAV2S1 and lysed targets expressing HLA-A2 and the Melan-A/MART-1 peptide: AAGIGILTV. Polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) analysis showed that the Melan-A/MART-1-specific clones were predominant in the bulk culture prior to cloning. However, the tumour progressed in vivo even in the presence of these tumour cell-lytic clones. Using the anti-Melan-A/MART-1 MoAb (A-103), we noted that Melan-A/MART-1 expression on three melanoma cell lines varied considerably during in vitro culture, in the absence of T cell immunoselection, relative to cell density. Tumour cells which spontaneously decreased Melan-A/MART-1 expression were less susceptible to specific TIL lysis. Melan-A/MART-1 expression and susceptibility to lysis increased in cells cultured at lower density. These data suggest that modulation of tumour antigen may account for tumour progression in the presence of tumour cell- lytic T lymphocytes. The observations suggest a possible explanation for the common finding of Melan-A/MART-1-specific lytic TIL in clinically progressing melanomas, as well as a possible pathway for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)11-18
Number of pages8
JournalClinical and Experimental Immunology
Volume119
Issue number1
DOIs
StatePublished - Feb 5 2000
Externally publishedYes

Keywords

  • Cytotoxic T lymphocytes
  • Melan-A/MART-1
  • Melanoma
  • PCR-SSCP
  • T cell receptor
  • Tumour-infiltrating lymphocytes

ASJC Scopus subject areas

  • Immunology

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  • Cite this

    Ramirez-Montagut, T., Andrews, D. M., Ihara, A., Pervaiz, S., Pandolfi, F., Van Den Elsen, P. J., Waitkus, R., Boyle, L. A., Hishii, M., & Kurnick, J. T. (2000). Melanoma antigen recognition by tumour-infiltrating T lymphocytes (TIL): Effect of differential expression of Melan-A/MART-1. Clinical and Experimental Immunology, 119(1), 11-18. https://doi.org/10.1046/j.1365-2249.2000.01089.x