Lack of tumor recognition by hTERT peptide 540-548-specific CD8(+) T cells from melanoma patients reveals inefficient antigen processing.

Details

Serval ID
serval:BIB_5B44AAEC8764
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Lack of tumor recognition by hTERT peptide 540-548-specific CD8(+) T cells from melanoma patients reveals inefficient antigen processing.
Journal
European journal of immunology
Author(s)
Ayyoub M., Migliaccio M., Guillaume P., Liénard D., Cerottini J.C., Romero P., Lévy F., Speiser D.E., Valmori D.
ISSN
0014-2980
Publication state
Published
Issued date
2001
Peer-reviewed
Oui
Volume
31
Number
9
Pages
2642-51
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
Telomerase is a ribonucleoprotein complex responsible for the maintenance of the length of the telomeres during cell division, which is active in germ-line cells as well as in the vast majority of tumors but not in most normal tissues. The wide expression of the human telomerase catalytic subunit (hTERT) in tumors makes it an interesting candidate vaccine for cancer. hTERT-derived peptide 540-548 (hTERT(540)) has been recently shown to be recognized in an HLA-A*0201-restricted fashion by T cell lines derived from peptide-stimulated peripheral blood mononuclear cells (PBMC) from healthy donors. As a first step to the inclusion of this peptide in immunotherapy clinical trials, it is crucial to assess hTERT(540)-specific T cell reactivity in cancer patients as well as the ability of hTERT-specific CD8(+) T lymphocytes to recognize and lyse hTERT-expressing target cells. Here, we have analyzed the CD8(+) T cell response to peptide hTERT(540) in HLA-A*0201 melanoma patients by using fluorescent HLA-A*0201/hTERT(540) peptide tetramers. HLA-A*0201/hTERT(540) tetramer(+) CD8(+) T cells were readily detected in peptide-stimulated PBMC from a significant proportion of patients and could be isolated by tetramer-guided cell sorting. hTERT(540)-specific CD8(+) T cells were able to specifically recognize HLA-A*0201 cells either pulsed with peptide or transiently transfected with a minigene encoding the minimal epitope. In contrast, they failed to recognize hTERT-expressing HLA-A*0201(+) target cells. Furthermore, in vitro proteasome digestion studies revealed inadequate hTERT processing. Altogether, these results raise questions on the use of hTERT(540) peptide for cancer immunotherapy.
Keywords
Antigen Presentation, Antigens, Neoplasm, Cell Line, Clone Cells, Cysteine Endopeptidases, Cytotoxicity Tests, Immunologic, Epitopes, Flow Cytometry, HLA-A Antigens, Humans, Melanoma, Multienzyme Complexes, Peptide Fragments, Proteasome Endopeptidase Complex, T-Lymphocytes, Cytotoxic, Telomerase, Transfection, Tumor Cells, Cultured
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 11:17
Last modification date
20/08/2019 14:14
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