PD-L1 EXPRESSION CORRELATES WITH TUMOR INFILTRATING LYMPHOCYTES AND BETTER PROGNOSIS IN PATIENTS WITH HPV-NEGATIVE HEAD AND NECK SQUAMOUS CELL CARCINOMAS

Abstract

Introduction: The importance of immune tumor microenvironment in the prognosis of patients with head and neck squamous carcinomas (HNSCC) is increasingly recognized. We analyzed the prognostic relevance of PD-L1 and PD-1 expression in relation to the infiltration by CD8+ and FOXP3+ tumor infiltrating lymphocytes (TILs). Methods: Samples from 372 surgically treated HPV-negative HNSCC patients were evaluated by immunohistochemistry for PD-L1 expression (both tumor proportion score -TPS- and combined proportion score -CPS-), PD-1 expression in immune cells, and density of infiltrating CD8+ and FOXP3+ TILs. PD-L1 expression and CD8+ TIL density were combined to establish the type of tumor microenvironment. Results: 29.5% cases exhibited PD-L1 TPS positivity (≥1%), whereas PD-L1 CPS positivity (≥ 1%) was observed in 40% cases. 47.5% cases showed positive PD-1 expression (≥ 1%). PD-L1 and PD-1 positivity correlated with a high density of both CD8+ and FOXP3+ TILs. In univariate analysis, PD-L1 TPS positivity (P=0.026), PD-L1 CPS positivity (P=0.004), high density of CD8+ TIL (P=0.001), and high density of FOXP3+ TIL (P=0.004) were associated with a better disease-specific survival (DSS). However, in multivariate analysis only high density of CD8+ TIL was associated with a better DSS (P=0.002). The type of tumor microenvironment correlated with DSS (P=.008), with the better DSS observed in cases with type I (PD-L1 CPS positivity and high density of CD8+ TIL). Conclusions: High infiltration by CD8+ TIL is associated with better survival outcomes. Positive PD-L1 expression correlates with a high infiltration by TILs, explaining its association with better prognosis.