Detection and long-term in vivo monitoring of individual tumor-specific T cell clones in patients with metastatic melanoma.
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.
Michalek
Jaroslav
J
Cell Immunotherapy Center, Masaryk University, Brno, Czech Republic. jmichalek@fnbrno.cz
Kocak
Ivo
I
Fait
Vuk
V
Zaloudik
Jan
J
Hajek
Roman
R
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
D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes