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首页> 外文期刊>British Journal of Cancer >Fas ligand mediates immune privilege and not inflammation in human colon cancer, irrespective of TGF-|[beta]| expression
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Fas ligand mediates immune privilege and not inflammation in human colon cancer, irrespective of TGF-|[beta]| expression

机译:与TGF- |β|无关,Fas配体介导人结肠癌的免疫特权而不是炎症。表达

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Many cancers express Fas ligand (FasL/CD95L) in vivo, and can kill lymphoid cells by Fas-mediated apoptosis in vitro. However, overexpression of recombinant FasL in murine tumour allografts revealed a potential antitumour effect of FasL, via recruitment of neutrophils. Transforming growth factor-β1 (TGF-β1) could inhibit these neutrophil-stimulatory effects of FasL. In the present study, we sought to determine directly whether FasL contributes to immune privilege or tumour rejection in human colon cancers in vivo, and whether TGF-β1 regulates FasL function. Serial tumour sections were immunostained for FasL and TGF-β1. Neutrophils and tumour infiltrating lymphocytes (TILs) were detected by immunohistochemistry for lactoferrin and CD45, respectively. Apoptotic TIL were identified by dual staining for TUNEL/CD45. FasL expression by nests of tumour cells was associated with a mean four-fold depletion of TILs (range 1.8–33-fold, n=16, Pn=14, Pn=16), with FasL expression by tumour nests associated with a mean two-fold decrease in neutrophils, irrespective of TGF-β1 expression. Together, our results suggest that tumour-expressed FasL is inhibitory rather than stimulatory towards antitumour immune responses.
机译:许多癌症在体内表达Fas配体(FasL / CD95L),并且可以在Fas介导的细胞凋亡中杀死淋巴细胞。然而,重组FasL在鼠肿瘤同种异体移植物中的过表达揭示了通过募集嗜中性粒细胞的FasL的潜在抗肿瘤作用。转化生长因子-β1(TGF-β1)可以抑制FasL的这些中性粒细胞刺激作用。在本研究中,我们试图直接确定FasL是否有助于体内人结肠癌的免疫特权或肿瘤排斥,以及TGF-β1是否调节FasL功能。对系列肿瘤切片进行FasL和TGF-β1免疫染色。通过免疫组织化学分别检测乳铁蛋白和CD45的嗜中性粒细胞和肿瘤浸润淋巴细胞(TIL)。通过对TUNEL / CD45进行双重染色来鉴定凋亡的TIL。肿瘤细胞巢的FasL表达与TIL的平均四倍减少有关(范围为1.8-33倍,n = 16,Pn = 14,Pn = 16),肿瘤巢的FasL表达与平均两次相关不论TGF-β1表达如何,嗜中性白血球减少了两倍。总之,我们的结果表明,肿瘤表达的FasL具有抑制作用,而不是对抗肿瘤免疫反应的刺激作用。

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