A novel autocrine pathway of tumor escape from immune recognition: Melanoma cell lines produce a soluble protein that diminishes expression of the gene encoding the melanocyte lineage Melan-A/MART-1 antigen through down-modulation of its promoter

J. T. Kurnick, T. Ramirez-Montagut, L. A. Boyle, David Andrews, F. Pandolfi, P. J. Durda, D. Butera, I. S. Dunn, E. M. Benson, S. J P Gobin, P. J. Van den Elsen

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Abstract

We have observed that malignant melanoma cells produce a soluble protein factor(s), which down-regulates melanocyte lineage Melan-A/MART-1 Ag expression by melanoma cells with concomitant loss of recognition by Melan-A/MART-1-specific T cells. This down-modulation of Melan-A/MART-1 expression, which we refer to as "Ag silencing," is mediated via its minimal promoter, whereas the promoter for the restricting Ag-presenting HLA-A2 molecule is not affected. Significantly, this Ag silencing is reversible, as removal of factor-containing supernatants from Melan-A/MART-1-expressing cells results in up-regulation of the promoter for the gene encoding this Ag, and renewed expression of the protein. We have evaluated over 20 known factors, none of which accounts for the Ag-silencing activity of the melanoma cell culture supernatants. The existence of this autocrine pathway provides an additional novel explanation for melanoma tumor progression in vivo in the presence of CTL specific for this melanocyte lineage Ag. These observations may have important implications for Melan-A/MART-1-specific CTL-mediated immunotherapy of melanoma tumors.

Original languageEnglish
Pages (from-to)1204-1211
Number of pages8
JournalJournal of Immunology
Volume167
Issue number3
StatePublished - Aug 1 2001
Externally publishedYes

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MART-1 Antigen
Tumor Escape
Melanocytes
Melanoma
Gene Expression
Cell Line
Proteins
HLA-A2 Antigen
Immunotherapy
Neoplasms
Up-Regulation
Down-Regulation
Cell Culture Techniques
T-Lymphocytes
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

A novel autocrine pathway of tumor escape from immune recognition : Melanoma cell lines produce a soluble protein that diminishes expression of the gene encoding the melanocyte lineage Melan-A/MART-1 antigen through down-modulation of its promoter. / Kurnick, J. T.; Ramirez-Montagut, T.; Boyle, L. A.; Andrews, David; Pandolfi, F.; Durda, P. J.; Butera, D.; Dunn, I. S.; Benson, E. M.; Gobin, S. J P; Van den Elsen, P. J.

In: Journal of Immunology, Vol. 167, No. 3, 01.08.2001, p. 1204-1211.

Research output: Contribution to journalArticle

Kurnick, J. T. ; Ramirez-Montagut, T. ; Boyle, L. A. ; Andrews, David ; Pandolfi, F. ; Durda, P. J. ; Butera, D. ; Dunn, I. S. ; Benson, E. M. ; Gobin, S. J P ; Van den Elsen, P. J. / A novel autocrine pathway of tumor escape from immune recognition : Melanoma cell lines produce a soluble protein that diminishes expression of the gene encoding the melanocyte lineage Melan-A/MART-1 antigen through down-modulation of its promoter. In: Journal of Immunology. 2001 ; Vol. 167, No. 3. pp. 1204-1211.
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