Tumor-infiltrating CD8C lymphocytes predict different clinical outcomes in organ- and non-organ-confined urothelial carcinoma of the bladder following radical cystectomy

Abstract

Tumor-infiltrating lymphocytes (TILs) are associated with better clinical outcomes in many tumors. TILs represent a cell-mediated immune response against the carcinoma. CD8C TILs are a crucial component of cell-mediated immunity. The significance of CD8C TILs has not been reported respectively in organ- and non-organ-confined urothelial carcinoma (UC) of the bladder. We explored the prognostic value of CD8C TILs in the two groups. The presence of CD8CTILs was assessed by immunohistochem- ical staining of whole tissue sections from 75 organ and 51 non-organ-confined disease patients with long-term follow-up, and its correlation with clinicopathological features and overall survival (OS) was determined. The CD8C TIL immunohistochemical staining score was 0 (<1%), 1 (≥1%), 2 (≥5%), or 3 (≥10%) based on the percentage of positively stained cells out of total cells. A patient was considered CD8 negative if the score was 0. There were no associations between CD8C TILs and age, sex, nuclear grade, and adjuvant or neoadjuvant chemotherapy in organ- and non-organ-confined disease. The presence of CD8C TILs was seen more frequently in pTa-1 than pT2 stage (p =033) in organ-confined disease. No associations between CD8C TILs and pT stage, pN stage were found in non-organ-confined disease. CD8C TILs were associated with better OS (log-rank test, P =036) in non-organ-confined disease, but with poorer OS (log-rank test, P =040) in organ-confined disease by the Kaplan-Meier method. In multivariate analysis, CD8CTILs were an independent favorable prognostic factor in non-organ-confined disease, but were an independent unfavorable prognostic factor in organ-confined disease. These results suggest that CD8C TILs have clinically significant anti-tumor activity in non-organ-confined disease, but may have pro-tumor activity in organ-confined disease. Therefore, we should be cautious if CD8C TILs are aimed to be exploited in the treatment of bladder cancer.