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*
Department of Tumor Cell Biology, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark;
Department of Pathology, Herlev Hospital, Copenhagen, Denmark; and
Department of Dermatology, School of Medicine, Würzburg, Germany
It is well established that melanoma cells express Ags that are recognized by autologous T cells in vitro. Tumor-infiltrating lymphocytes in situ comprise clonotypic T cells, suggesting that their expansion is driven by Ag stimulation. Still, little is known about the detailed characteristics of the in situ T cell response. In the present study, we scrutinized this response by analyzing multiple metastatic lesions for the presence of clonotypic T cells. This approach was chosen to distinguish whether the clonal T cell expansion occurs as a systemic or localized phenomenon. TCR clonotype mapping of six s.c. metastases from two patients revealed the presence of multiple (from 40 to >60) clonotypic T cells in all lesions. Clonotypic T cells were present in TCR ß-variable regions expressed both at high and low levels. Comparison of the T cell clonotypes present in different lesions from individual patients demonstrated that, in general, clonotypes were exclusively detected in a single lesion. Hence, anti-melanoma T cell responses are much more heterogeneous than previously anticipated and accommodate a predominance of strictly localized T cell clonotypes.
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