An Expanded Peripheral T Cell Population to a Cytotoxic T Lymphocyte (CTL)-defined, Melanocyte-specific Antigen in Metastatic Melanoma Patients Affects Generation of Peptide-specific CTLs but Does Not Overcome Tumor Escape from Immune Surveillance in Metastatic Lesions

It is not known if immune response to T cell-defined human histocompatibility leukocyte antigen (HLA) class I-restricted melanoma antigens leads to an expanded peripheral pool of T cells in all patients, affects cytotoxic T lymphocyte (CTL) generation, and correlates with anti-tumor response in metastatic lesions. To this end, a limiting dilution analysis technique was developed that allowed us to evaluate the same frequency of peptide-specific T cells as by staining T cells with HLA-peptide tetrameric complexes. In four out of nine patients, Melan-A/Mart-1 sub(27-35)-specific CTL precursors (CTLp) were greater than or equal to 1/2,000 peripheral blood lymphocytes and found mostly or only in the CD45RO super(+) memory T cell subset. In the remaining five patients, a low (