title: In situ T cell responses against melanoma comprise high numbers of locally expanded T cell clonotypes.
abstract: 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 beta-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.
authors.affiliation: Department of Tumor Cell Biology, Institute of Cancer Biology, Danish Cancer Society, Copenhagen. ps@cancer.dk
authors.forename: P
authors.initials: P
authors.lastname: thor Straten
authors.forename: P
authors.initials: P
authors.lastname: Guldberg
authors.forename: K
authors.initials: K
authors.lastname: Grønbaek
authors.forename: M R
authors.initials: MR
authors.lastname: Hansen
authors.forename: A F
authors.initials: AF
authors.lastname: Kirkin
authors.forename: T
authors.initials: T
authors.lastname: Seremet
authors.forename: J
authors.initials: J
authors.lastname: Zeuthen
authors.forename: J C
authors.initials: JC
authors.lastname: Becker
mesh_terms: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology; D002999:Clone Cells; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta