PVR/TIGIT and PD-L1/PD-1 expression predicts survival and enlightens combined immunotherapy in lung squamous cell carcinoma

PVR/TIGIT and PD-L1/PD-1 axes play essential roles in tumor immune evasion and could be potential targets for combined immunotherapy. We aimed to evaluate the expression status of the above-mentioned immune markers in lung squamous cell carcinoma (LUSC), and investigate their survival impact and relevance with the immune microenvironment and clinicopathological features. We retrospectively collected specimens from 190 LUSC patients, who underwent pulmonary surgeries, and we performed immunohistochemistry assays of PVR, TIGIT, PD-L1, PD-1 and CD8. In our cohort, the positive rate of PVR was 85.8%, which was much higher than the positive rate of PD-L1 at 26.8%. A total of 32 (16.8%) patients demonstrated co-expression of PVR/PD-L1. High TIGIT density was correlated with positive PD-L1 expression, high PD-1 density, and high CD8 density (PD-L1, P=0.033; PD-1, P<0.001; CD8, P<0.001), and positive PVR expression was correlated with positive PD-L1 expression (P=0.046). High TIGIT density and high PVR/TIGIT expression were correlated with advanced TNM stage (TIGIT density, P=0.020; PVR/TIGIT expression, P=0.041). Patients with positive PVR expression, high TIGIT density, high PVR/TIGIT expression and PVR/PD-L1 co-expression exhibited a significantly worse prognosis (PVR, P=0.038; TIGIT, P=0.027; PVR/TIGIT, P=0.014; PVR/PD-L1, P=0.018). Multivariate analysis demonstrated that PVR/PD-L1 co-expression (Hazard ratio [HR], 1.756, 95% CI, 1.152-2.676, P=0.009) was an independent prognostic factor in LUSC patients. In conclusion, we demonstrated the expression status of PVR/TIGIT and PD-L1/PD-1 in LUSC. PVR/PD-L1 co-expression was an independent prognostic factor in LUSC patients and may serve as a potential predictive biomarker for dual-targeting immunotherapy.