Tumor infiltrating lymphocytes in seminoma lesions comprise clonally expanded cytotoxic T cells
Tumor infiltrating lymphocytes in seminoma lesions comprise clonally expanded cytotoxic T cells
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DOI：
10.1002/ijc.21894
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发表时间：
2006-08-15
影响因子：
6.4
通讯作者：
Straten, Per thor
中科院分区：
文献类型：
--
作者：
Hadrup, Sine Reker;Braendstrup, Otto;Straten, Per thor
精原细胞瘤病变的特征是活跃的炎性浸润，其中含有CD 4和CD 8 T细胞，这具有预后意义。然而，乳腺癌细胞是否表达经典T细胞识别所需的HLA分子仍然存在争议。在本研究中，我们进行了肿瘤浸润淋巴细胞（TIL）的分子，表型和功能特性的肿瘤病变。T细胞受体克隆型定位显示，在大多数病变中存在克隆扩增的T细胞。TIL的细胞毒性能力通过CD 107 a的表达来指示，CD 107 a是最近描述的细胞溶解活性的替代标志物。事实上，与外周血单核细胞相比，TIL中CD 107 a阳性细胞的频率显著更高。此外，CD 107 a阳性TIL的荧光激活细胞分选允许比较克隆型T细胞受体指纹，并证明扩增的克隆表达这种细胞毒性标记物的能力，表明在肿瘤部位的细胞毒性活性。通过原位颗粒酶B表达证实细胞毒性。此外，通过用多聚体HLA-肽复合物染色。我们可以证明在TIL中存在法师-3特异性T细胞。总之，特异性和功能性T细胞反应在乳腺癌中起作用，表明炎性浸润确实参与了肿瘤的免疫控制。(c)2006 Wiley-Liss，Inc.
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. (c) 2006 Wiley-Liss, Inc.