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-γ T cells, TCRβ 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 CB8 T cell clones with frequencies of 10 to 10 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. Copyright © 2007 by The American Association of Immunologists, Inc.