Prognostic and clinicopathological significance of PD-L1 and tumor infiltrating lymphocytes in hypopharyngeal squamous cell carcinoma.

OBJECTIVES: Limited information is available regarding programmed death-ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) in hypopharyngeal squamous cell carcinoma (HPSCC). Therefore, we investigated the expression of PD-L1 and the volume of TILs in HPSCC to determine whether these biomarkers were associated with patient clinicopathologic characteristics and prognosis. Furthermore, we explored p16 status and analyzed its possible correlations with clinical outcomes. METHODS: Tissues of 111 HPSCC patients were immunohistochemically analyzed for PD-L1, CD8, CD4, and Foxp3 expression to assess the microenvironment. We also assessed the p16 status. The expression of PD-L1 and TILs were analyzed with respect to patient clinicopathologic variables and prognosis. RESULTS: Twenty-four (21.6%) patients had PD-L1 expression in >/=1% of tumor cells. PD-L1 expression was significantly correlated with a high level of TILs (P < 0.05). Kaplan-Meier analysis showed that higher CD8+ and FoxP3+ TIL infiltration was strongly associated with superior overall survival (OS, P = 0.005 and P = 0.008) and disease-free survival (DFS, P = 0.015 and P = 0.048). Univariate and multivariate analyses confirmed that CD8+ TIL exhibited strong prognostic significance. The combination of PD-L1(+) with CD8(high) expression was a prognostic factor and was associated with better OS (P = 0.025). Moreover, p16 positivity was detected in five patients (4.5%) and was only occasionally involved in HPSCC. CONCLUSION: Our findings indicate that high CD8 and FoxP3 expression in HPSCC contributes to longer patient survival. Although PD-L1 expression was not associated with outcome, PD-L1 positivity in combination with CD8(high) expression may have greater predictive potential.