Tumor infiltrating lymphocytes in seminoma lesions comprise clonally expanded cytotoxic T cells.
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.
Tumor Immunology Group, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark.
Sine Reker
SR
Hadrup
Otto
O
Braendstrup
Grete Krag
GK
Jacobsen
Svend
S
Mortensen
Lars Østergaard
LØ
Pedersen
Tina
T
Seremet
Mads Hald
MH
Andersen
Jürgen C
JC
Becker
Per Thor
PT
Straten
D000328:Adult; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D002999:Clone Cells / Q000166:cytology* / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic; D053804:Granzymes; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D018239:Seminoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D012697:Serine Endopeptidases / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000276:immunology*
D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; D052118:Lysosomal-Associated Membrane Protein 1; D011948:Receptors, Antigen, T-Cell; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases