Gewählte Publikation:
Straten, PT; Guldberg, P; Gronbaek, K; Hansen, MR; Kirkin, AF; Seremet, T; Zeuthen, J; Becker, JC.
In situ T cell responses against melanoma comprise high numbers of locally expanded T cell clonotypes.
J Immunol. 1999; 163(1):443-447
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- Co-Autor*innen der Med Uni Graz
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Becker Jürgen Christian
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- 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.
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Antigens, Neoplasm -
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Cell Differentiation - immunology
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Clone Cells -
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Electrophoresis, Polyacrylamide Gel -
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Humans -
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Lymphocyte Count -
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Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - metabolism
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Melanoma - immunology Melanoma - metabolism
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Neoplasm Proteins - biosynthesis
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Receptors, Antigen, T-Cell, alpha-beta - biosynthesis Receptors, Antigen, T-Cell, alpha-beta - genetics Receptors, Antigen, T-Cell, alpha-beta - isolation and purification
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Reverse Transcriptase Polymerase Chain Reaction -
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Sequence Analysis, DNA -
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Skin Neoplasms - immunology Skin Neoplasms - metabolism
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T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism
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Transcription, Genetic - immunology
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Tumor Markers, Biological - biosynthesis