Abstract
Targeting T-Cell Immunoreceptor with Ig and ITIM domain-poliovirus receptor (PVR) pathway is a potential therapeutic strategy in lung cancer. We analyzed the expression of PVR and programmed death ligand-1 (PD-L1) in surgically resected squamous cell lung carcinoma (SQCC) and determined its prognostic significance. We collected archival surgical specimens and data of 259 patients with SQCC at Yonsei Cancer Center (1998–2020). Analysis of variance was used to analyze the correlations between PVR and PD-L1 expression and patient characteristics. Kaplan–Meier curves were used to estimate recurrence-free survival (RFS) and overall survival (OS). Most patients were male (93%); the majority were diagnosed with stage 1 (47%), followed by stage 2 (29%) and stage 3 (21%). Overexpression of PVR resulted in a significantly shorter median RFS and OS (P = 0.01). PD-L1 expression was not significant in terms of prognosis. Patients were subdivided into four groups based on low and high PVR and PD-L1 expression. Those expressing high levels of PVR and PD-L1 had the shortest RFS (P = 0.03). PVR overexpression is associated with a poor prognosis in surgically resected SQCC. Inhibition of PVR as well as PD-L1 may help overcome the lack of response to immune checkpoint monotherapy.
Highlights
Targeting T-Cell Immunoreceptor with Ig and ITIM domain-poliovirus receptor (PVR) pathway is a potential therapeutic strategy in lung cancer
We found that the programmed death ligand-1 (PD-L1) and PVR clusters were independently expressed as per TCGA RNAsequencing data
PD-L1hi/PVRhi status was correlated with the worst recurrence-free survival (RFS), signifying that both
Summary
Targeting T-Cell Immunoreceptor with Ig and ITIM domain-poliovirus receptor (PVR) pathway is a potential therapeutic strategy in lung cancer. We analyzed the expression of PVR and programmed death ligand-1 (PD-L1) in surgically resected squamous cell lung carcinoma (SQCC) and determined its prognostic significance. Overexpression of PVR resulted in a significantly shorter median RFS and OS (P = 0.01). Patients were subdivided into four groups based on low and high PVR and PD-L1 expression. Those expressing high levels of PVR and PD-L1 had the shortest RFS (P = 0.03). PVR overexpression is associated with a poor prognosis in surgically resected SQCC. With distinct clinicopathological features, such as a lack of targetable mutations, higher incidence in older individuals, and advanced or metastatic disease at diagnosis, patients with SQCC have a shorter lifespan than those with other. The first-line treatment options for advanced SQCC were limited to platinumdoublet chemotherapy, with a median survival of 8–11 m
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