Liu Jinʼe, Xie Xiaoxue, Xuan Chunxiao, Li Tingting, Wang Lanlan, Teng Lianghong, Liu Jun
Department of Pathology, Xuanwu Hospital, Beijing, China.
Pancreas. 2018 Jul;47(6):725-731. doi: 10.1097/MPA.0000000000001059.
UNLABELLED: V-domain immunoglobulin suppressor of T-cell activation (VISTA) is constitutively expressed in hematopoietic lineage and is highly up-regulated in tumor infiltrated myeloid cells and regulatory T-cells in animal models. However, its expression in human pancreatic tumor microenvironment remains unknown. In this research, we aimed at the expression of VISTA in human pancreatic cancer samples. METHODS: We performed immunohistochemistry to determine VISTA expression in human pancreatic cancer samples. RESULTS: We found that 88.46% of the patients showed high-density infiltration of polymorphonuclear neutrophils and mononuclear immune cells with up-regulated expression of VISTA in cancer tissues, especially in the necrotic foci. Interestingly, it was minimally expressed in pancreatic cancerous cells and was not detectable in either normal ducts or islet cells in cancerous or normal pancreatic tissues. CONCLUSIONS: We conclude that VISTA is predominantly expressed and up-regulated in the high-density infiltrated immune cells but minimal in human pancreatic cancerous cells. Our results for the first time highlight pancreatic immunosuppressive tumor microenvironment contributed by VISTA and its potential as a prominent target for pancreatic cancer immunotherapy.
未标记:T细胞活化的V结构域免疫球蛋白抑制因子(VISTA)在造血谱系中组成性表达,在动物模型的肿瘤浸润髓样细胞和调节性T细胞中高度上调。然而,其在人胰腺肿瘤微环境中的表达仍不清楚。在本研究中,我们旨在研究VISTA在人胰腺癌样本中的表达。 方法:我们进行免疫组织化学以确定VISTA在人胰腺癌样本中的表达。 结果:我们发现88.46%的患者癌组织中多形核中性粒细胞和单核免疫细胞呈高密度浸润,VISTA表达上调,尤其是在坏死灶中。有趣的是,它在胰腺癌细胞中表达极少,在癌性或正常胰腺组织的正常导管或胰岛细胞中均未检测到。 结论:我们得出结论,VISTA主要在高密度浸润的免疫细胞中表达并上调,但在人胰腺癌细胞中表达极少。我们的结果首次突出了VISTA促成的胰腺免疫抑制肿瘤微环境及其作为胰腺癌免疫治疗突出靶点的潜力。
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