HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by thor Straten, P. Articles by Becker, J. C. Search for Related Content PubMed PubMed Citation Articles by thor Straten, P. Articles by Becker, J. C.

In Situ T Cell Responses Against Melanoma Comprise High Numbers of Locally Expanded T Cell Clonotypes¹

Per thor Straten^2,*, Per Guldberg^*, Kirsten Grønbæk^*,, Mia Riise Hansen^*, Alexei F. Kirkin^*, Tina Seremet^*, Jesper Zeuthen^* and Jürgen C. Becker

^* 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.