Tissue Homing and Persistence of Defined Antigen-Specific CD8+ Tumor-Reactive T-Cell Clones in Long-Term Melanoma Survivors

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 tumo...

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Published in:Journal of investigative dermatology 2007-03, Vol.127 (3), p.622-629
Main Authors: Le Gal, Frédérique-Anne, Widmer, Valérie M., Dutoit, Valérie, Rubio-Godoy, Verena, Schrenzel, Jacques, Walker, Paul R., Romero, Pedro J., Valmori, Danila, Speiser, Daniel E., Dietrich, Pierre-Yves
Format: Article
Language:English
Subjects:
Antigens, Neoplasm - immunology
Biological and medical sciences
CD8-Positive T-Lymphocytes - immunology
Cell Differentiation
Dermatology
Disease Progression
Flow Cytometry
Humans
Immunotherapy
Leukocytes, Mononuclear - cytology
Male
Medical sciences
Melanoma - blood
Melanoma - immunology
Middle Aged
Neoplasm Metastasis
Neoplasm Proteins - immunology
Phenotype
Time Factors
Treatment Outcome
Tumors of the skin and soft tissue. Premalignant lesions
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Summary: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.
ISSN:0022-202X
1523-1747
DOI:10.1038/sj.jid.5700580