Schweyer S, Soruri A, Baumhoer D, Peters J, Cattaruzza M, Radzun H J, Fayyazi A
Department of Pathology, Georg-August-University Göttingen, Germany.
J Pathol. 2002 May;197(1):89-97. doi: 10.1002/path.1094.
Tumour-infiltrating T lymphocytes (TILs) possess discrepant properties ranging from anti- to protumour activities. Understanding precisely which mechanisms navigating T lymphocytes into the tumour site will help to further the anti-tumour or to disrupt the pro-tumour activities of TILs. The present study asked what enables TILs to migrate into testicular germ cell tumours (TGCTs). TILs were characterized and the expression of a large panel of T-lymphocyte-attracting chemokines was investigated in 21 TGCT cases. Flow cytometry revealed that approximately 80% of TGCT-infiltrating T lymphocytes express CXCR3, a receptor for the chemokine interferon-inducible protein-10 (IP-10). RT-PCR and immunohistochemistry indicated that IP-10 was the only chemokine investigated which was constantly expressed in TGCT. As IP-10 was found to be expressed by endothelial cells of TGCT-associated blood vessels, the question arose whether the IP-10-regulating cytokine interferon-gamma (IFNgamma) is produced by tumour cells and if so, whether tumour-derived IFNgamma can induce IP-10 in endothelial cells. Applying in situ hybridization, IFNgamma transcripts were found in neoplastic germ cells. Analyses of two TGCT cell lines indicated that the tumour cells not only express IFNgamma mRNA, but also produce and secrete IFNgamma protein; tumour-derived IFNgamma provokes IP-10 expression and secretion by endothelial cells in vitro, as assessed by PCR and ELISA. Together, the data suggest that neoplastic germ cells secret IFNgamma and thereby stimulate tumour-associated endothelial cells to express IP-10, which contributes to the recruitment of CXCR3+ T lymphocytes to the site of TGCTs.
肿瘤浸润性T淋巴细胞（TILs）具有从抗肿瘤到促肿瘤活性的不同特性。准确了解哪些机制引导T淋巴细胞进入肿瘤部位将有助于增强TILs的抗肿瘤活性或破坏其促肿瘤活性。本研究探讨了是什么使TILs能够迁移到睾丸生殖细胞肿瘤（TGCTs）中。对21例TGCT病例中的TILs进行了表征，并研究了大量T淋巴细胞吸引趋化因子的表达。流式细胞术显示，约80%的TGCT浸润性T淋巴细胞表达CXCR3，这是趋化因子干扰素诱导蛋白10（IP-10）的受体。逆转录聚合酶链反应（RT-PCR）和免疫组织化学表明，IP-10是所研究的唯一在TGCT中持续表达的趋化因子。由于发现IP-10由TGCT相关血管的内皮细胞表达，因此出现了一个问题，即调节IP-10的细胞因子干扰素-γ（IFNγ）是否由肿瘤细胞产生，如果是，肿瘤来源的IFNγ是否能在内皮细胞中诱导IP-10表达。应用原位杂交技术，在肿瘤性生殖细胞中发现了IFNγ转录本。对两种TGCT细胞系的分析表明，肿瘤细胞不仅表达IFNγ mRNA，还产生并分泌IFNγ蛋白；通过PCR和酶联免疫吸附测定（ELISA）评估，肿瘤来源的IFNγ在体外可刺激内皮细胞表达和分泌IP-10。总之，数据表明肿瘤性生殖细胞分泌IFNγ，从而刺激肿瘤相关内皮细胞表达IP-10，这有助于将CXCR3+ T淋巴细胞募集到TGCT部位。
