Tumor infiltrating lymphocytes in seminoma lesions comprise clonally expanded cytotoxic T cells
Autor: | Mads Hald Andersen, Tina Seremet, Lars Østergaard Pedersen, S. Mortensen, Otto Brændstrup, Jürgen C. Becker, Per thor Straten, Sine Reker Hadrup, Grete Krag Jacobsen |
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Rok vydání: | 2006 |
Předmět: |
Adult
Cancer Research Pathology medicine.medical_specialty Receptors Antigen T-Cell Granzymes Immune system Lymphocytes Tumor-Infiltrating Antigen Antigens Neoplasm Lysosomal-Associated Membrane Protein 1 medicine Cytotoxic T cell Humans biology Tumor-infiltrating lymphocytes Histocompatibility Antigens Class I Serine Endopeptidases Seminoma Middle Aged medicine.disease Clone Cells Granzyme B Gene Expression Regulation Neoplastic Phenotype Oncology Granzyme biology.protein Cancer research Cancer/testis antigens T-Lymphocytes Cytotoxic |
Zdroj: | International journal of cancer. 119(4) |
ISSN: | 0020-7136 |
Popis: | Seminoma lesions are characterized by a brisk inflammatory infiltrate containing both CD4 and CD8 T cells, which is of prognostic significance. However, whether seminoma cells express the HLA molecules required for classical T-cell recognition remains controversial. In the present study, we conducted a molecular, phenotypical and functional characterization of tumor infiltrating lymphocytes (TILs) from seminoma lesions. T-cell receptor clonotype mapping demonstrated the presence of clonally expanded T cells in the majority of the lesions. The cytotoxic capacity of TILs was indicated by expression of CD107a, which is a recently described surrogate marker for cytolytic activity. Indeed, the frequency of CD107a positive cells was substantially higher in TILs when compared to peripheral blood mononuclear cells. Moreover, fluorescence activated cell sorting of CD107a positive TILs allowed comparison of the clonotypic T-cell receptor fingerprint and demonstrated the ability of expanded clones to express this cytotoxic marker, suggesting cytotoxic activity at the tumor site. The cytotoxicity was confirmed by in situ granzyme B expression. Furthermore, by staining with multimeric HLA-peptide complexes, we could demonstrate the presence of Mage-3 specific T cells among TILs. In summary, specific and functional T-cell responses are operative in seminoma, indicating that the inflammatory infiltrate is indeed involved in the immunological control of the tumor. |
Databáze: | OpenAIRE |
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