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

Citation
M. Ayyoub et al., Lack of tumor recognition by hTERT peptide 540-548-specific CD8(+) T cellsfrom melanoma patients reveals inefficient antigen processing., EUR J IMMUN, 31(9), 2001, pp. 2642-2651
Citations number
32
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
EUROPEAN JOURNAL OF IMMUNOLOGY
ISSN journal
0014-2980 → ACNP
Volume
31
Issue
9
Year of publication
2001
Pages
2642 - 2651
Database
ISI
SICI code
0014-2980(200109)31:9<2642:LOTRBH>2.0.ZU;2-C
Abstract
Telomerase is a ribonucleoprotein complex responsible for the maintenance o f 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 norma l tissues. The wide expression of the human telomerase catalytic subunit (h TERT) in tumors makes it an Interesting candidate vaccine for cancer. hTERT -derived peptide 540-548 (hTERT(540)) has been recently shown to be recogni zed in an HLA-A*0201-restricted fashion by T cell lines derived from peptid e-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 Gell reactivity in c ancer patients as well as the ability of hTERT-specific CD8(+) T lymphocyte s to recognize and lyse hTERT-expressing target cells. Here, we have analyz ed the CD8+ T cell response to peptide hTERT(540) in HLA-A*0201 melanoma pa tients 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 iso lated by tetramer-guided cell sorting. hTERT(540)-specific CD8(+) T cells w ere able to specifically recognize HLA-A*0201 cells either pulsed with pept ide or transiently transfected with a minigene encoding the minimal epitope . In contrast, they failed to recognize hTERT-expressing HLA-A*0201(+) targ et cells. Furthermore, in vitro proteasome digestion studies revealed inade quate hTERT processing. Altogether, these results raise questions on the us e of hTERT(540) peptide for cancer immunotherapy.