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高内皮静脉是肝内胆管癌切除术后具有预后意义的免疫相关生物标志物。

High endothelial venule is a prognostic immune-related biomarker in patients with resected intrahepatic cholangiocarcinoma.

机构信息

Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Department of Hepatobiliary Surgery, Drum Tower Clinical College of Nanjing Medical University, Nanjing, China.

出版信息

Cell Prolif. 2023 Dec;56(12):e13513. doi: 10.1111/cpr.13513. Epub 2023 Jul 3.

Abstract

Having been reported to be a crucial prognostic factor in solid tumours, the role of high endothelial venule (HEV) in intrahepatic cholangiocarcinoma (ICC) remains unclear, however. The data of ICC and healthy individuals were downloaded from the Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) databases. Meanwhile, a cutting-edge ICC high-resolution spatial transcriptome was also acquired before these data were comprehensively analysed using bioinformatics approaches. Moreover, 95 individuals with ICC who had undergone resection surgery were enrolled in this study to investigate the relationship between HEV and tumour microenvironment (TME) applying immunohistochemistry and multiple immunofluorescence techniques. The high-HEV subtype contains rich immune infiltrates including tertiary lymphoid structure (TLS), CD8+ T cells, and CD20+ B cells. Furthermore, HEV and TLS exhibited a strong relationship of spatial colocalization. Correlated with improved prognostic outcomes in ICC, the high-HEV subtype could be an independent prognostic indicator for individuals with ICC. This study revealed the association of HEV with immune function and observed a strong spatial colocalization correlation between HEV and TLS. Moreover, correlated with immunotherapeutic response, HEV could improve prognostic outcomes, which may be a potential indicator of immunotherapy pathology in ICC.

摘要

高内皮静脉(HEV)被报道为实体瘤中一个关键的预后因素,但其在肝内胆管癌(ICC)中的作用尚不清楚。ICC 和健康个体的数据从基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)数据库中下载,然后使用生物信息学方法对这些数据进行全面分析。此外,本研究还纳入了 95 名接受手术切除的 ICC 患者,应用免疫组织化学和多免疫荧光技术研究 HEV 与肿瘤微环境(TME)之间的关系。高 HEV 亚型富含免疫浸润,包括三级淋巴结构(TLS)、CD8+T 细胞和 CD20+B 细胞。此外,HEV 和 TLS 具有强烈的空间共定位关系。与 ICC 的改善预后结果相关,高 HEV 亚型可以作为 ICC 患者的独立预后指标。本研究揭示了 HEV 与免疫功能的关联,并观察到 HEV 与 TLS 之间存在强烈的空间共定位相关性。此外,与免疫治疗反应相关,HEV 可以改善预后结果,这可能是 ICC 免疫治疗病理学的一个潜在指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5247/10693183/ab3bba371e40/CPR-56-e13513-g004.jpg

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