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浸润非小细胞肺癌的CD8+ T细胞的免疫激活状态

Immune activation status of CD8+ T cells infiltrating non-small cell lung cancer.

作者信息

Trojan Andreas, Urosevic Mirjana, Dummer Reinhard, Giger Robin, Weder Walter, Stahel Rolf A

机构信息

Department of Oncology, University Hospital Zürich, Rämistrasse 100, CH-8091 Zurich, Switzerland.

出版信息

Lung Cancer. 2004 May;44(2):143-7. doi: 10.1016/j.lungcan.2003.11.004.

DOI:10.1016/j.lungcan.2003.11.004
PMID:15084378
Abstract

In a variety of human cancers, the presence of tumor-infiltrating T lymphocytes (TILs) is associated with tumor regression and favorable prognosis. Local interferon (IFN)-gamma secretion from activated T cells is supposed to induce a specific immune response leading to tumor-specific cytotoxicity. Nonetheless, significance and properties of TILs still remains controversial in lung cancer patients. We determined CD8+ T cell counts in 31 patients with non-small cell lung cancer (NSCLC) by immunohistochemistry, and assessed T-cell immune activation status in a subset of patients by measuring IFN-gamma mRNA expression by quantitative PCR (TaqMan). Semi-quantitative immunohistochemical analysis revealed significantly higher CD8+ T cell counts within the tumor as when compared to the invasive margin. CD8+ T cells immune activation status, represented in the IFN-gamma/CD8 mRNA ratio, correlated with the median number of CD8+ T cells presented at the tumor-host interface. Neither tumor histology and grade, nor CD8+ T cell counts and IFN-gamma/CD8 ratio could demonstrate an influence on overall survival in these patients. Our results indicate that CD8+ T cells infiltrating the tumor cell nests may be inadequately activated and thus incapable of mounting an effective anti-tumor immune response.

摘要

在多种人类癌症中,肿瘤浸润性T淋巴细胞(TILs)的存在与肿瘤消退及良好预后相关。活化T细胞分泌的局部干扰素(IFN)-γ被认为可诱导特异性免疫反应,从而导致肿瘤特异性细胞毒性。尽管如此,TILs在肺癌患者中的意义和特性仍存在争议。我们通过免疫组织化学法测定了31例非小细胞肺癌(NSCLC)患者的CD8 + T细胞计数,并通过定量PCR(TaqMan)测量IFN-γ mRNA表达,评估了部分患者的T细胞免疫激活状态。半定量免疫组织化学分析显示,与肿瘤浸润边缘相比,肿瘤内CD8 + T细胞计数显著更高。以IFN-γ/CD8 mRNA比值表示的CD8 + T细胞免疫激活状态,与肿瘤-宿主界面处CD8 + T细胞的中位数相关。肿瘤组织学类型、分级、CD8 + T细胞计数及IFN-γ/CD8比值均未显示对这些患者的总生存期有影响。我们的结果表明,浸润肿瘤细胞巢的CD8 + T细胞可能未得到充分激活,因此无法产生有效的抗肿瘤免疫反应。

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