title: Detection and long-term in vivo monitoring of individual tumor-specific T cell clones in patients with metastatic melanoma.
abstract: We investigated the presence of individual melanoma-specific T cell clones in patients with metastatic melanoma. Ten patients were examined for the presence of melanoma-reactive T cells using dendritic cells loaded with autologous tumor cells. Their specificity was tested using nonradioactive cytotoxicity test. Individual immunodominant T cell clones were identified by the clonotypic assay that combines in vitro cell culture, immunomagnetic sorting of activated IFN-gamma(+) T cells, TCRbeta locus-anchored RT-PCR, and clonotypic quantitative PCR. All patients had detectable melanoma-reactive T cells in vitro. Expanded melanoma-reactive T cells demonstrated specific cytotoxic effect against autologous tumor cells in vitro. Three patients experienced objective responses, and their clinical responses were closely associated with the in vivo expansion and long-term persistence of individual CD8(+) T cell clones with frequencies of 10(-6) to 10(-3) of all circulating CD8(+) T cells. Five patients with progressive disease experienced no or temporary presence of circulating melanoma-reactive T cell clones. Thus, circulating immunodominant CD8(+) T cell clones closely correlate with clinical outcome in patients with metastatic melanoma.
authors.affiliation: Cell Immunotherapy Center, Masaryk University, Brno, Czech Republic. jmichalek@fnbrno.cz
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Michalek
authors.forename: Ivo
authors.initials: I
authors.lastname: Kocak
authors.forename: Vuk
authors.initials: V
authors.lastname: Fait
authors.forename: Jan
authors.initials: J
authors.lastname: Zaloudik
authors.forename: Roman
authors.initials: R
authors.lastname: Hajek
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D002999:Clone Cells / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000032:analysis / Q000276:immunology*; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes / Q000032:analysis / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology* / Q000556:secondary; D008875:Middle Aged; D015166:Monitoring, Immunologic; D009360:Neoplastic Cells, Circulating / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology* / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes