Document Detail


Tissue homing and persistence of defined antigen-specific CD8+ tumor-reactive T-cell clones in long-term melanoma survivors.
MedLine Citation:
PMID:  17039243     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Frédérique-Anne Le Gal; Valérie M Widmer; Valérie Dutoit; Verena Rubio-Godoy; Jacques Schrenzel; Paul R Walker; Pedro J Romero; Danila Valmori; Daniel E Speiser; Pierre-Yves Dietrich
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-10-12
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  127     ISSN:  1523-1747     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-14     Completed Date:  2007-03-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  622-9     Citation Subset:  IM    
Affiliation:
Laboratory of Tumor Immunology, Division of Oncology, Department of Internal Medicine, University Hospital, Geneva, Switzerland. frederique-anne.legal@hcuge.ch
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MeSH Terms
Descriptor/Qualifier:
Antigens, Neoplasm / immunology
CD8-Positive T-Lymphocytes / immunology*
Cell Differentiation
Disease Progression
Flow Cytometry
Humans
Immunotherapy
Leukocytes, Mononuclear / cytology
Male
Melanoma / blood,  immunology*
Middle Aged
Neoplasm Metastasis
Neoplasm Proteins / immunology
Phenotype
Time Factors
Treatment Outcome
Chemical
Reg. No./Substance:
0/Antigens, Neoplasm; 0/MAGEA10 protein, human; 0/Neoplasm Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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