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血吸虫相关性膀胱肿瘤微环境中T淋巴细胞群体的免疫组化模式

Immunohistochemical pattern of T lymphocytes population within bilharzial-associated bladder neoplasm microenvironment.

作者信息

El-Aal Amany Ahmed Abd, Emran Ashraf Mohamed, Al-Antably Abeer Said, El Saftawy Enas Ali, Bayoumy Ibrahim R, Hassan Nabila Salah, Badawi Manal

机构信息

Parasitology Department, Faculty of Medicine, Cairo University, Egypt.

Urosurgery Department, Faculty of Medicine, Cairo University, Egypt.

出版信息

Int J Immunopathol Pharmacol. 2015 Jun;28(2):209-17. doi: 10.1177/0394632015584733. Epub 2015 Apr 29.

DOI:10.1177/0394632015584733
PMID:25926591
Abstract

The present work aimed to investigate the cellular and immunochemical pattern of T cells population in biopsy material from chronic schistosomiasis haematobium Egyptian patients complicated with bladder cancer. Digital real-time quantitative photocytometry was applied to auto-analyze 29 stained tissue sections from cases and 17 controls using STAT4, GATA3, FOXP3, and CD8 markers specific for Th1, Th2, T regulatory, and T cytotoxic cells, respectively. Area percentage showed significant high level of GATA, followed by FOXP3 and low level of both STAT and CD8 was reported. Tissue samples from five healthy bladder tissues showed significant lower optical density (OD) values. Tissue samples from 12 non-bilharzial bladder cancers showed variable OD values, reflecting wide disparity in the control group.Our results hypothesized an exclusive pattern of T population in long standing complicated schistosomiasis haematobium. Our cases were poorly controlled by unbalanced Th1/Th2 in which Th2 was dominated. FOXP3 increased significantly, however, failed to downregulate Th2, instead, the relation between Th1 and T cytotoxic was forcibly limited by the high level of FOXP3, resulting in loss of their power in defending the host against both parasite and carcinogenic changes. These results provide more clarification for the immune evasion process played by the parasite and tumor cells under the supervision of T regulatory cells. Additionally a critical role of FOXP3 is suggested in manipulating STAT4 and CD8 in favor of malignant transformation in this life-threatening parasite.

摘要

本研究旨在调查埃及慢性血吸虫病血尿患者并发膀胱癌活检材料中T细胞群体的细胞和免疫化学模式。应用数字实时定量光细胞术,使用分别针对Th1、Th2、调节性T细胞和细胞毒性T细胞的STAT4、GATA3、FOXP3和CD8标记物,对29例病例和17例对照的染色组织切片进行自动分析。面积百分比显示GATA水平显著升高,其次是FOXP3,而STAT和CD8水平较低。来自五个健康膀胱组织的组织样本显示光密度(OD)值显著较低。来自12例非血吸虫性膀胱癌的组织样本显示OD值各不相同,反映了对照组的广泛差异。我们的结果推测,在长期复杂的埃及血吸虫病中,T细胞群体存在独特模式。我们的病例中,Th1/Th2失衡,Th2占主导,控制不佳。FOXP3显著增加,但未能下调Th2,相反,Th1与细胞毒性T细胞之间的关系因FOXP3水平升高而受到强烈限制,导致它们在抵御寄生虫和致癌变化方面的能力丧失。这些结果为寄生虫和肿瘤细胞在调节性T细胞监督下的免疫逃逸过程提供了更多解释。此外,FOXP3在操纵STAT4和CD8以促进这种危及生命的寄生虫的恶性转化方面的关键作用也被提出。

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