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Terheyden, P; Schrama, D; Pedersen, LO; Andersen, MH; Kampgen, E; Straten, PT; Becker, JC.
Longitudinal analysis of MART-1/HLA-A2-reactive T cells over the course of melanoma progression
SCAND J IMMUNOL. 2003; 58(5): 566-571. Doi: 10.1046/j.1365-3083.2003.01324.x
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Leading authors Med Uni Graz: Becker Jürgen Christian
Co-authors Med Uni Graz: Schrama David
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Abstract:: An HLA-A2-positive patient with advanced stage IV melanoma was vaccinated with dendritic cells (DCs) pulsed with melanoma antigens, whereby the rapid progression of disease stalled for a period of 10 months. Monitoring of the cellular immune response against one of the vaccinated HLA-A2-restricted epitopes demonstrated both induction and subsequent decline in the number of interferon-gamma (IFN-gamma)-producing MART-1-reactive cells present in the blood. Enumeration of reactive T cells by MART-126-35/HLA-A2 tetramer staining revealed an induction of such cells after three vaccinations and a subsequent decline that most prominent at times of rapid disease progression. However, a substantial number of reactive cells were present even when no MART-1 reactivity was detectable by functional assays. Isolation of such MART-126-35-reactive T cells by means of peptide/HLA-A2-coated magnetic beads demonstrated the persistence of a TCRVbeta14+ T-cell clone in this population over the whole observation period. Intracellular fluorescence-activated cell sorter staining of such TCRVbeta14+ T cells for IFN-gamma and interleukin-2 after maximal stimulation with phorbol 12-myristate 13-acetate/ionomycin revealed an impairment in their capacity to produce cytokines at the end of the observation period. Thus, functional changes of individual T-cell clones, e.g. clonal exhaustion, seem to be responsible for the known discrepancy between functional and phenotype assays for immune monitoring of tumour patients.
Find related publications in this database (using NLM MeSH Indexing): Antigens, Neoplasm -; Disease Progression -; HLA-A2 Antigen - immunology; Humans -; Interferon-gamma - biosynthesis; Interleukin-2 - biosynthesis; Longitudinal Studies -; Male -; Melanoma - immunology; Middle Aged -; Neoplasm Proteins - immunology; Receptors, Antigen, T-Cell - physiology; Receptors, Antigen, T-Cell, alpha-beta - analysis; T-Lymphocytes - immunology