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Tissue homing and persistence of defined antigen-specific CD8+ tumor-reactive T-cell clones in long-term melanoma survivors.
- Source :
-
The Journal of investigative dermatology [J Invest Dermatol] 2007 Mar; Vol. 127 (3), pp. 622-9. Date of Electronic Publication: 2006 Oct 12. - Publication Year :
- 2007
-
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.
- Subjects :
- Antigens, Neoplasm immunology
Cell Differentiation
Disease Progression
Flow Cytometry
Humans
Immunotherapy
Leukocytes, Mononuclear cytology
Male
Melanoma blood
Middle Aged
Neoplasm Metastasis
Neoplasm Proteins immunology
Phenotype
Time Factors
Treatment Outcome
CD8-Positive T-Lymphocytes immunology
Melanoma immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1523-1747
- Volume :
- 127
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of investigative dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 17039243
- Full Text :
- https://doi.org/10.1038/sj.jid.5700580