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A shift in the phenotype of melan-A-specific CTL identifies melanoma patients with an active tumor-specific immune response
A shift in the phenotype of melan-A-specific CTL identifies melanoma patients with an active tumor-specific immune response
- Source :
- Scopus-Elsevier
- Publication Year :
- 2016
-
Abstract
- In a significant proportion of melanoma patients, CTL specific for the melan-A26/7β35 epitope can be detected in peripheral blood using HLA-A2/peptide tetramers. However, the functional capacity of these CTL has been controversial, since although they prove to be effective killers after in vitro expansion, in some patients they have blunted activation responses ex vivo. We used phenotypic markers to characterize melan-A tetramer+ cells in both normal individuals and melanoma patients, and correlated these markers with ex vivo assays of CTL function. Melanoma patients with detectable melan-A tetramer+ cells in peripheral blood fell into two groups. Seven of thirteen patients had a CCR7+ CD45R0β CD45RA+ phenotype, the same as that found in some healthy controls, and this phenotype was associated with a lack of response to melan-A peptide ex vivo. In the remaining six patients, melan-A tetramer+ cells were shifted toward a CCR7β CD45R0+ CD45RAβ phenotype, and responses to melan-A peptide could be readily demonstrated ex vivo. When lymph nodes infiltrated by melan-A-expressing melanoma cells were examined, a similar dichotomy emerged. These findings demonstrate that activation of melan-A-specific CTL occurs in only some patients with malignant melanoma, and that only patients with such active immune responses are capable of responding to Ag in ex vivo assays.
- Subjects :
- Adult
Male
Immunology
Epitopes, T-Lymphocyte
chemical and pharmacologic phenomena
CD8-Positive T-Lymphocytes
Biology
Epitope
Immunophenotyping
Lymphocytes, Tumor-Infiltrating
MART-1 Antigen
Immune system
Antigens, Neoplasm
Cell Movement
Tumor Cells, Cultured
medicine
Humans
Immunology and Allergy
Melanoma
Aged
Cell Line, Transformed
Aged, 80 and over
Middle Aged
medicine.disease
Lymphocyte Subsets
In vitro
Neoplasm Proteins
CTL
Female
Lymph Nodes
Ex vivo
T-Lymphocytes, Cytotoxic
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Scopus-Elsevier
- Accession number :
- edsair.doi.dedup.....34a004eb8b4c13a805a73e25a2748feb