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首页> 外文期刊>British Journal of Cancer >Impaired T-bet-pSTAT1 α and perforin-mediated immune responses in the tumoral region of lung adenocarcinoma
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Impaired T-bet-pSTAT1 α and perforin-mediated immune responses in the tumoral region of lung adenocarcinoma

机译：肺腺癌肿瘤区域T-bet-pSTAT1 α和穿孔素介导的免疫反应受损

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Background: In spite of modern therapies for non-small-cell lung cancer (NSCLC), prognosis for many patients is still poor and survival rates are low. Immunotherapy is the possibility to improve the lung immune response surrounding the tumour. However, this approach requires detailed understanding of the local immune-responses of NSCLC patients. Methods: We analysed samples from three different regions within the lungs of NSCLC patients, whereas we distinguished between patients suffering from adenocarcinoma and squamous cell carcinoma. Expression of type 1 T helper (Th1)/type 1 cytotoxic (Tc1) factors was assessed by quantitative real-time PCR, western blot analyses or immunohistochemistry. Cytotoxic cell activity of CD8~(+)T cells was determined via co-culture with autologous tumour cells and apoptosis assay. Results: We found decreased levels of the transcription factor T-box expressed in T cells (T-bet or Tbx21) and of the downstream activated IFN- γ -dependent pSTAT1 α isoform in the lung tumour areas of patients with NSCLC as compared with tumour-free control regions. In these patients, reduced T-bet and pSTAT1 α levels were found associated with increased immunosuppressive markers like cytotoxic T lymphocyte-associated protein 4, programmed cell death 1 and with a suppression of the Th1 cell cytokine production and Tc1 cell activity. Conclusions: These findings confirm a central role of T-bet in targeted immunotherapy for patients with NSCLC.
机译：背景：尽管有针对非小细胞肺癌（NSCLC）的现代疗法，但许多患者的预后仍然很差，生存率很低。免疫疗法可能会改善肿瘤周围的肺部免疫反应。但是，这种方法需要详细了解NSCLC患者的局部免疫反应。方法：我们分析了非小细胞肺癌患者肺内三个不同区域的样本，而我们区分了患有腺癌和鳞状细胞癌的患者。通过实时定量PCR，蛋白质印迹分析或免疫组织化学评估1型T辅助因子（Th1）/ 1型细胞毒性（Tc1）因子的表达。通过与自体肿瘤细胞共培养和凋亡测定法测定CD8〜（+）T细胞的细胞毒活性。结果：我们发现与肿瘤相比，NSCLC患者肺肿瘤区域中T细胞（T-bet或Tbx21）中表达的转录因子T-box和下游激活的IFN-γ依赖性pSTAT1α亚型的表达水平降低了。 -无控制区域。在这些患者中，发现降低的T-bet和pSTAT1α水平与增加的免疫抑制标记（例如细胞毒性T淋巴细胞相关蛋白4），程序性细胞死亡1以及Th1细胞细胞因子生成和Tc1细胞活性的抑制有关。结论：这些发现证实了T-bet在非小细胞肺癌患者靶向免疫治疗中的重要作用。

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