CD103+ Tumor Infiltrating Lymphocytes Predict a Favorable Prognosis in Urothelial Cell Carcinoma of the Bladder

• Published in: The Journal of urology Vol. 194; no. 2; pp. 556 - 562
• Main Authors: Wang, Bo, Wu, Shaoxu, Zeng, Hong, Liu, Zhuowei, Dong, Wen, He, Wang, Chen, Xu, Dong, Xiaoliang, Zheng, Limin, Lin, Tianxin, Huang, Jian
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2015
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; antigens; Antigens, CD - immunology; Antigens, CD - metabolism; Biomarkers, Tumor - analysis; carcinoma; Carcinoma, Transitional Cell - immunology; Carcinoma, Transitional Cell - mortality; Carcinoma, Transitional Cell - pathology; CD8; China - epidemiology; Disease-Free Survival; Female; Fluorescent Antibody Technique; Humans; Immunohistochemistry; Integrin alpha Chains - immunology; Integrin alpha Chains - metabolism; Kaplan-Meier Estimate; lymphocytes; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Lymphocytes, Tumor-Infiltrating - pathology; Male; Middle Aged; Neoplasm Staging; Prognosis; Proportional Hazards Models; Retrospective Studies; Survival Rate - trends; tumor infiltrating; urinary bladder; Urinary Bladder - immunology; Urinary Bladder - metabolism; Urinary Bladder - pathology; Urinary Bladder Neoplasms - immunology; Urinary Bladder Neoplasms - mortality; Urinary Bladder Neoplasms - pathology; Urology; Young Adult; China; bacillus Calmette-Guérin; tumor infiltrating lymphocyte; INT; muscle invasive bladder cancer; natural killer; recurrence-free survival; overall survival; RFS; ST; lymphocytes; tumor infiltrating; intratumor; OS; urinary bladder; BCG; stroma; antigens; prognosis; bladder urothelial cell carcinoma; carcinoma; UCB; CD8; TIL; MIBC; NK
• ISSN: 0022-5347; 1527-3792
• DOI: 10.1016/j.juro.2015.02.2941

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.