Intratumoral expression of programmed death ligand 1 (PD-L1) in patients with clear cell renal cell carcinoma (ccRCC).

Abstract

The immunological checkpoints of programmed death 1 and its ligand (PD-L1) are currently in focus as novel therapeutic targets in renal cell carcinoma (RCC). The aim of this study was to evaluate the prognostic association of PD-L1 expression in clear cell (cc) RCC with clinical parameters, tumor aggressiveness and overall survival (OS). Patients who underwent renal surgery due to RCC between 1994 and 2003 were retrospectively evaluated. Tumor specimens were analyzed for PD-L1 expression by immunohistochemistry. One hundred and seventy-seven ccRCC patients were eligible for analysis, in which 140 (79.1%) were negative and 37 (20.9%) were positive for PD-L1 expression. PD-L1 positivity was associated with female gender (p=0.001), lymph node metastasis (p=0.004), distant metastasis (p=0.002), higher AJCC stage (p=0.004), as well as advanced disease (pT3/4 and/or N+ and/or M1) (p<0.001). Kaplan-Meier analysis revealed a significantly diminished 5- and 10-year overall survival of 46.7 and 28.3% for PD-L1(+) compared to PD-L1(-) tumors with 66 and 53.4% (p=0.005), respectively. Univariate analysis showed a significant negative association of OS with PD-L1 positivity [p=0.005; HR: 2 (95% CI 1.2-3.3)], even though PD-L1 positivity only tends to predict independently the OS using multivariate analyses [p=0.066; HR: 1.6 (95% CI 0.98-2.7)]. PD-L1 expression in ccRCC is associated with parameters of aggressiveness, as well as with poor OS, even though PD-L1 status was not identified as a significant independent prognostic parameter. However, further studies in larger cohorts are warranted.