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

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.

Keywords: CD8; antigens; carcinoma; lymphocytes; prognosis; tumor infiltrating; urinary bladder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • Biomarkers, Tumor / analysis
  • Carcinoma, Transitional Cell / immunology*
  • Carcinoma, Transitional Cell / mortality
  • Carcinoma, Transitional Cell / pathology
  • China / epidemiology
  • Disease-Free Survival
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Immunohistochemistry
  • Integrin alpha Chains / immunology*
  • Integrin alpha Chains / metabolism
  • Kaplan-Meier Estimate
  • 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
  • Urinary Bladder / immunology*
  • Urinary Bladder / metabolism
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms / immunology*
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology
  • Young Adult


  • Antigens, CD
  • Biomarkers, Tumor
  • Integrin alpha Chains
  • alpha E integrins