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 language | English |
|---|---|
| Pages (from-to) | 1204-1211 |
| Number of pages | 8 |
| Journal | Journal of Immunology |
| Volume | 167 |
| Issue number | 3 |
| State | Published - Aug 1 2001 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - A novel autocrine pathway of tumor escape from immune recognition
T2 - 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
AU - Kurnick, J. T.
AU - Ramirez-Montagut, T.
AU - Boyle, L. A.
AU - Andrews, David
AU - Pandolfi, F.
AU - Durda, P. J.
AU - Butera, D.
AU - Dunn, I. S.
AU - Benson, E. M.
AU - Gobin, S. J P
AU - Van den Elsen, P. J.
PY - 2001/8/1
Y1 - 2001/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0035422746&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035422746&partnerID=8YFLogxK
M3 - Article
C2 - 11466335
AN - SCOPUS:0035422746
VL - 167
SP - 1204
EP - 1211
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 3
ER -