Distribution and prognostic significance of CD8+ T cells in urothelial cell carcinoma of the bladder

Objective The aim of this study was to investigate the distribution and clinical significance of CD8+ T cells in bladder cancer tissues in situ. Methods Immunohistochemistry were used to examine the distribution of CD8+ T cells in bladder cancer tissues, which were obtained from January 2003 to December 2009 from 302 patients.Among all the patients, 262 were male while 40 were female; mean age is 60 years; tumor size ≤ 3 cm was in 235 and tumor size > 3 cm was in 67; Unifocal tumor was in 214 and multifocal tumors were in 88.Amount of tumor stage Ta–T1 was 212 and T2–T4 was 90.Sixteen patients have lymph node metastasis.Histological low grade was diagnosed in 175 and histological high grade was diagnosed in 127.According to the differences between anatomic structure and cellular composition, bladder tumor tissues can be classified to two localization patterns: (1) intratumoral regions, defined as tumor cell nests; (2) stromal regions, defined as stromal areas that lack direct contact with tumor cells.Therefore, we divided 302 bladder cancer patients into two groups based on the median frequency of intratumoral CD8+ T cells (median, 3/×400 high resolution) and stromal CD8+ T cells (median, 37/×400 high resolution), respectively.χ2 analysis was used to evaluated the correlation between CD8+ T cell density and clinicalpathological variables.Kaplan–Meier analysis and Cox proportional hazards regression models were applied to estimate overall survival (OS). Results CD8+ T cells were predominantly located in the intratumoral regions (mean, 14 ± 2/×400 high resolution) rather than in associated stromal regions (mean, 50± 3/×400 high resolution, P<0.05). The density of intratumoral CD8+ T cells was inversely associated with age(P=0.026), tumor size (P<0.05) and tumor stage (P<0.05), and could represent a favorable prognostic predictor of OS (HR=0.427, P=0.003). However, the density of stromal CD8+ T cells was positively associated with age(P=0.004) and histological grade (P<0.01), and could represent an adverse prognostic predictor of OS (HR=2.206, P=0.009). Conclusions Our findings suggest that intratumoral/ stromal CD8+ T cells could potentially serve as favorable/ adverse prognostic markers for bladder cancer patients, respectively. Key words: Bladder cancer; CD8; T cells; Prognosis