Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China.
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China.
J Urol. 2015 Aug;194(2):556-62. doi: 10.1016/j.juro.2015.02.2941. Epub 2015 Mar 6.
PURPOSE: CD8(+) TILs at different tumor sites have diverse clinical attributes, which might result from distinct tumor microenvironments that promote differentiation into distinct subsets. However, only a few markers have been identified that can define CD8(+) T-cell subsets. CD103 is a marker of tissue resident memory CD8(+) T cells. In this retrospective study we investigated the cellular source and clinical significance of CD103 expression in urothelial cell carcinoma of bladder tissues in situ. MATERIALS AND METHODS: Immunohistochemistry and immunofluorescence were used to identify the cellular source of CD103 in bladder urothelial cell carcinoma tissues. Kaplan-Meier analysis and Cox proportional hazards regression models were applied to estimate overall and recurrence-free survival in 302 patients with bladder urothelial cell carcinoma. RESULTS: CD8(+) T cells but not natural killer cells accounted for most CD103 expressing cells in bladder urothelial cell carcinoma tissues. Notably CD103(+) cells were predominantly located in intratumor regions rather than in associated stroma (p < 0.0001). The density of intratumor CD103(+) TILs was inversely associated with tumor size (p < 0.0001) and could represent a favorable prognostic predictor of overall and recurrence-free survival (p = 0.002 and 0.011, respectively). Moreover, intratumor CD103(+) TILs were positively associated with the expression of cognate ligand E-cadherin in intratumor regions of bladder urothelial cell carcinoma tissues (p = 0.008). CONCLUSIONS: Our findings suggest that CD8(+) T cells might have a significant role in tumor immunity by expressing CD103 in intratumor regions of bladder urothelial cell carcinoma tissues. Intratumor CD103(+) TILs could potentially serve as a prognostic marker in patients with bladder urothelial cell carcinoma.
目的:不同肿瘤部位的 CD8(+)TIL 具有不同的临床特征,这可能是由于不同的肿瘤微环境促进其分化为不同的亚群。然而,目前仅有少数标记物可用于定义 CD8(+)T 细胞亚群。CD103 是组织驻留记忆 CD8(+)T 细胞的标志物。在这项回顾性研究中,我们研究了 CD103 在原位膀胱尿路上皮癌组织中的细胞来源及其临床意义。
材料和方法:使用免疫组织化学和免疫荧光法鉴定膀胱尿路上皮癌组织中 CD103 的细胞来源。Kaplan-Meier 分析和 Cox 比例风险回归模型用于估计 302 例膀胱尿路上皮癌患者的总生存期和无复发生存期。
结果:CD8(+)T 细胞而非自然杀伤细胞是膀胱尿路上皮癌组织中大多数 CD103 表达细胞的来源。值得注意的是,CD103(+)细胞主要位于肿瘤内区域,而不是相关的基质中(p < 0.0001)。肿瘤内 CD103(+)TIL 密度与肿瘤大小呈负相关(p < 0.0001),可作为总生存期和无复发生存期的有利预后预测指标(p = 0.002 和 0.011)。此外,肿瘤内 CD103(+)TIL 与膀胱尿路上皮癌组织肿瘤内区域中同源配体 E-钙黏蛋白的表达呈正相关(p = 0.008)。
结论:我们的研究结果表明,CD8(+)T 细胞通过在膀胱尿路上皮癌组织肿瘤内区域表达 CD103,可能在肿瘤免疫中发挥重要作用。肿瘤内 CD103(+)TIL 可能成为膀胱尿路上皮癌患者的预后标志物。
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