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目的:探讨von Hippel-Lindau（VHL）综合征遗传性肾癌中免疫细胞浸润的特点及其与临床病理和预后的关系。方法:收集2010年至2019年于北京大学第一医院泌尿外科确诊并进行手术治疗的VHL综合征肾癌患者的样本。对6对新鲜匹配的VHL综合征肾癌和癌旁组织进行RNA-Seq测序，利用TIP工具将RNA-Seq数据转换成14种免疫细胞的浸润数据，并进行分析比较。采用免疫组织化学染色方法在54对匹配的VHL综合征肾癌和癌旁组织的石蜡切片中来验证差异浸润免疫细胞表面标志物的表达情况，并分析其与患者临床病理及预后的关系。结果:与癌旁组织相比，VHL综合征肾癌中初始CD4 T细胞浸润水平显著下调（0.289±0.009比0.200±0.012，n P<0.001），记忆CD4 T细胞浸润水平显著上调（0.123±0.014比0.222±0.016，n P<0.001）。免疫组织化学染色结果显示，与癌旁组织相比，VHL综合征肾癌中CD45RA（初始CD4 T细胞标志物）表达明显降低（50.9±1.9比15.6±0.9，n P<0.001），CD45RO（记忆CD4 T细胞标志物）表达明显升高（22.2±1.1比80.8±4.3，n P<0.001）。此外，CD45RA低表达组和CD45RO高表达组具有更高的组织病理学分级、更晚的肿瘤分期和更低的无病生存率（均n P<0.01）。另外，CD45RA表达与VHL表达呈正相关（n r=0.693 3，n P<0.000 1），而CD45RO表达与VHL表达呈负相关（n r=-0.609 0，n P<0.000 1）。n 结论:初始CD4 T细胞和记忆CD4 T细胞可能是VHL综合征肾癌中特异性浸润的免疫细胞，且其浸润水平与VHL的表达和患者的预后密切相关。“,”Objective:To investigate the feature of immune cells infiltration in inherited renal carcinoma with von Hippel-Lindau (VHL) syndrome and their relationship with clinicopathological characteristics and prognosis.Methods:The samples were collected from patients with VHL syndrome renal carcinoma who were diagnosed and treated surgically at the Department of Urology, Peking University First Hospital from 2010 to 2019. RNA-Seq was performed on 6 pairs of VHL syndrome renal carcinoma and adjacent normal tissues. To identify the specific infiltrated immune cells, RNA-Seq data was converted into the infiltration data of 14 types of immune cells using the TIP tool. Immunohistochemical staining was used to verify the expression of the markers of these specific infiltrated immune cells in the paraffin sections of 54 paired VHL syndrome renal carcinoma and adjacent normal tissues, and to analyze their relationship with clinicopathological characteristics and prognosis.Results:Compared with adjacent normal tissues, CD4 Naive infiltration level was significantly down-regulated (0.289±0.009 vs 0.200±0.012,n P<0.001) and CD4 Memory infiltration level was significantly up-regulated (0.123±0.014 vs 0.222±0.016,n P<0.001) in VHL syndrome renal carcinoma. Immunohistochemical staining results showed that CD45RA (a CD4 Naive cell marker) expression was significantly reduced (50.9±1.9 vs 15.6±0.9,n P<0.001) and CD45RO (a CD4 Memory cell marker) expression was significantly increased (22.2±1.1 vs 80.8±4.3,n P<0.001) in VHL syndrome renal carcinoma. Besides, lower CD45RA expression and higher CD45RO expression were associated with higher histological grade, advanced tumor stage and shorter disease-free survival (alln P<0.01). In addition, CD45RA expression was positively correlated with VHL expression (n r=0.693 3, n P<0.000 1) and CD45RO expression was negatively correlated with VHL expression (n r=-0.609 0, n P<0.000 1).n Conclusions:This study found that CD4 Naive and CD4 Memory cells may be differentially infiltrated immune cells in VHL syndrome renal carcinoma, and their infiltration levels were associated with the expression of VHL and the prognosis of patients.