Relationship of tumor PD-L1 (CD274) expression with lower mortality in lung high-grade neuroendocrine tumor

Programmed death-ligand 1 (PD-L1) promotes immunosuppression by binding to PD-1 on T lymphocytes. Although tumor PD-L1 expression is a potential predictive marker of clinical response to anti-PD-1/PD-L1 therapy, little is known about its association with clinicopathological features, including prognosis, in high-grade neuroendocrine tumors (HGNETs), including small-cell lung carcinoma (SCLC) and large-cell neuroendocrine carcinoma (LCNEC), of the lung. We immunohistochemically examined the membranous of expression of PD-L1 in 115 consecutive surgical cases of lung HGNET (74 SCLC cases and 41 LCNEC cases). We examined the prognostic association of tumor PD-L1 positivity using the log-rank test as well as Cox proportional hazards regression models to calculate the hazard ratio (HR) for mortality. Programmed death-ligand 1 immunostaining (at least 5% tumor cells) was observed in 25 (21%) of the 115 HGNET cases. In a univariable analysis, PD-L1 positivity was associated with lower lung cancer-specific (univariable HR = 0.23; 95% confidence interval [CI] = 0.056-0.64; P = 0.0028) and overall (univariable HR = 0.28; 95% CI = 0.11-0.60; P = 0.0005) mortality. Additionally, in a multivariable analysis, PD-L1 positivity was independently associated with lower lung cancer-specific (multivariable HR = 0.24; 95% CI = 0.058-0.67; P = 0.0039) and overall (multivariable HR = 0.29; 95% CI = 0.11-0.61; P = 0.0006) mortality. Our study demonstrated the prevalence of PD-L1 positivity in lung HGNET cases, and the independent association of tumor PD-L1 positivity with lower mortality in lung HGNET cases. Further studies are needed to confirm our findings.