Detection and long-term in vivo monitoring of individual tumor-specific T cell clones in patients with metastatic melanoma |
| |
Authors: | Michalek Jaroslav Kocak Ivo Fait Vuk Zaloudik Jan Hajek Roman |
| |
Affiliation: | Cell Immunotherapy Center, Masaryk University, Brno, Czech Republic. jmichalek@fnbrno.cz |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|