Bo Wang1, Shaoxu Wu2, Hong Zeng3, Zhuowei Liu4, Wen Dong2, Wang He2, Xu Chen2, Xiaoliang Dong2, Limin Zheng5, Tianxin Lin6, Jian Huang7. 1. 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. 2. Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China. 3. Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China. 4. Department of Urology, Cancer Center, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China. 5. State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China. 6. 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. Electronic address: tianxinl@sina.com. 7. Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China. Electronic address: urolhj@sina.com.
Abstract
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.
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.
Authors: Ann Byrne; Peter Savas; Sneha Sant; Ran Li; Balaji Virassamy; Stephen J Luen; Paul A Beavis; Laura K Mackay; Paul J Neeson; Sherene Loi Journal: Nat Rev Clin Oncol Date: 2020-02-28 Impact factor: 66.675
Authors: Gang Xin; Achia Khatun; Paytsar Topchyan; Ryan Zander; Peter J Volberding; Yao Chen; Jian Shen; Chunmei Fu; Aimin Jiang; William A See; Weiguo Cui Journal: Cancer Immunol Res Date: 2019-11-12 Impact factor: 11.151