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肿瘤浸润免疫细胞中 VISTA 的表达与非肌肉浸润性膀胱癌的膀胱内复发时间短相关。

Expression of VISTA on tumor-infiltrating immune cells correlated with short intravesical recurrence in non-muscle-invasive bladder cancer.

机构信息

Department of Urology, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea.

Department of Pathology, Busan Paik Hospital, Inje University College of Medicine, 75 Bokji-ro, Busanjin-gu, Busan, 47392, Republic of Korea.

出版信息

Cancer Immunol Immunother. 2021 Nov;70(11):3113-3122. doi: 10.1007/s00262-021-02906-7. Epub 2021 Mar 26.

Abstract

V-domain immunoglobulin suppressor of T cell activation (VISTA) is an immune checkpoint molecule expressed in hematopoietic cells, granulocytes, macrophages, and monocytes. However, few studies to date have investigated VISTA expression, especially its clinical utility, in bladder cancer. The present retrospective study aimed to examine VISTA, programmed death ligand-1 (PD-L1), and CD45 expression by immunohistochemical and immunofluorescence staining of archived pathological tissue samples from 159 patients with primary bladder cancer. The correlation between VISTA expression in immune cells (ICs) and clinicopathologic variables including PD-L1 expression in ICs was examined. Briefly, the rates of VISTA-positive ICs and VISTA-positive tumor cells were 67.9% (108/159) and 30.8% (49/159), respectively. The VISTA expression in ICs of patients with bladder cancer, including those with non-muscle-invasive bladder cancer (NMIBC), was positively correlated with tumor stage, grade, size, and multiplicity. The VISTA expression in ICs was stronger in bladder cancer cases with PD-L1-positive ICs than in those with PD-L1-negative ICs (p < 0.001). The mean intravesical recurrence-free survival was shorter in NMIBC cases with VISTA-positive ICs than in those with VISTA-negative ICs (34.0 vs 39.9 months, p = 0.03, log-rank test). In this first study to investigate VISTA expression in bladder cancer, these results implicate VISTA as a potential immunotherapeutic target and immunologic biomarker in bladder cancer.

摘要

V 结构域免疫球蛋白抑制 T 细胞活化因子(VISTA)是一种在造血细胞、粒细胞、巨噬细胞和单核细胞中表达的免疫检查点分子。然而,迄今为止,很少有研究调查 VISTA 在膀胱癌中的表达,特别是其临床效用。本回顾性研究旨在通过对 159 例原发性膀胱癌患者存档的病理组织样本进行免疫组织化学和免疫荧光染色,检测 VISTA、程序性死亡配体 1(PD-L1)和 CD45 的表达。研究还检查了免疫细胞(ICs)中 VISTA 表达与包括 IC 中 PD-L1 表达在内的临床病理变量之间的相关性。简而言之,VISTA 阳性 ICs 和 VISTA 阳性肿瘤细胞的比例分别为 67.9%(108/159)和 30.8%(49/159)。膀胱癌患者 IC 中的 VISTA 表达,包括非肌层浸润性膀胱癌(NMIBC)患者,与肿瘤分期、分级、大小和多发性呈正相关。VISTA 在 ICs 中的表达在 PD-L1 阳性 ICs 的膀胱癌病例中强于 PD-L1 阴性 ICs(p<0.001)。VISTA 阳性 ICs 的 NMIBC 病例的膀胱内无复发生存率短于 VISTA 阴性 ICs 的病例(34.0 与 39.9 个月,p=0.03,对数秩检验)。在这项首次研究 VISTA 在膀胱癌中的表达的研究中,这些结果表明 VISTA 可能成为膀胱癌的潜在免疫治疗靶点和免疫生物标志物。

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Epidemiology of Bladder Cancer.膀胱癌流行病学
Med Sci (Basel). 2020 Mar 13;8(1):15. doi: 10.3390/medsci8010015.
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Role of Checkpoint Inhibition in Localized Bladder Cancer.局部膀胱癌的检查点抑制作用。
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VISTA expressed in tumour cells regulates T cell function.肿瘤细胞中表达的 VISTA 调节 T 细胞功能。
Br J Cancer. 2019 Jan;120(1):115-127. doi: 10.1038/s41416-018-0313-5. Epub 2018 Nov 9.

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