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

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Wang B., Wu S., Zeng H., Liu Z., Dong W., He W., Chen X., Dong X., Zheng L., Lin T., Huang J.

Journal of Urology 2015

Purpose: CD8<sup>+</sup> 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<sup>+</sup> T-cell subsets. CD103 is a marker of tissue resident memory CD8<sup>+</sup> 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<sup>+</sup> T cells but not natural killer cells accounted for most CD103 expressing cells in bladder urothelial cell carcinoma tissues. Notably CD103<sup>+</sup> cells were predominantly located in intratumor regions rather than in associated stroma (p <0.0001). The density of intratumor CD103<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> T cells might have a significant role in tumor immunity by expressing CD103 in intratumor regions of bladder urothelial cell carcinoma tissues. Intratumor CD103<sup>+</sup> TILs could potentially serve as a prognostic marker in patients with bladder urothelial cell carcinoma.

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