Tissue homing and persistence of defined antigen-specific CD8+ tumor-reactive T-cell clones in long-term melanoma survivors.

Details

Serval ID
serval:BIB_E2A0EDDC35A5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Tissue homing and persistence of defined antigen-specific CD8+ tumor-reactive T-cell clones in long-term melanoma survivors.
Journal
Journal of Investigative Dermatology
Author(s)
Le Gal F.A., Widmer V.M., Dutoit V., Rubio-Godoy V., Schrenzel J., Walker P.R., Romero P.J., Valmori D., Speiser D.E., Dietrich P.Y.
ISSN
1523-1747 (Electronic)
ISSN-L
0022-202X
Publication state
Published
Issued date
2007
Volume
127
Number
3
Pages
622-629
Language
english
Abstract
Tumor antigen-specific cytotoxic T cells (CTLs) play a major role in the adaptive immune response to cancers. This CTL response is often insufficient because of functional impairment, tumor escape mechanisms, or inhibitory tumor microenvironment. However, little is known about the fate of given tumor-specific CTL clones in cancer patients. Studies in patients with favorable outcomes may be very informative. In this longitudinal study, we tracked, quantified, and characterized functionally defined antigen-specific T-cell clones ex vivo, in peripheral blood and at tumor sites, in two long-term melanoma survivors. MAGE-A10-specific CD8+ T-cell clones with high avidity to antigenic peptide and tumor lytic capabilities persisted in peripheral blood over more than 10 years, with quantitative variations correlating with the clinical course. These clones were also found in emerging metastases, and, in one patient, circulating clonal T cells displayed a fully differentiated effector phenotype at the time of relapse. Longevity, tumor homing, differentiation phenotype, and quantitative adaptation to the disease phases suggest the contribution of the tracked tumor-reactive clones in the tumor control of these long-term metastatic survivor patients. Focusing research on patients with favorable outcomes may help to identify parameters that are crucial for an efficient antitumor response and to optimize cancer immunotherapy.
Keywords
Antigens, Neoplasm/immunology, CD8-Positive T-Lymphocytes/immunology, Cell Differentiation, Disease Progression, Flow Cytometry, Humans, Immunotherapy, Leukocytes, Mononuclear/cytology, Male, Melanoma/blood, Melanoma/immunology, Middle Aged, Neoplasm Metastasis, Neoplasm Proteins/immunology, Phenotype, Time Factors, Treatment Outcome
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 11:27
Last modification date
20/08/2019 16:06
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