Programmed Death-Ligand 1 Expression in Lymphovascular Tumor Emboli in Lung Cancer

Introduction: Programmed death-ligand 1 (PD-L1) expression determined by immunohistochemistry is the most widely used biomarker for predicting response to immune checkpoint inhibitors. The characteristics of PD-L1 expression in tumor cells inside lymphovascular spaces are largely unknown. Although PD-L1 expression in circulating tumor cells within vascular spaces had been studied, results were conflicting due to lack of standardized PD-L1 expression assessment. Methods: We investigated PD-L1 expression in lung cancer primary tumor tissue, lymphovascular tumor emboli, and lymph node metastasis using the standard PD-L1 immunohistochemistry 22C3 pharmDx assay. PD-L1 expression was scored in the primary tumor, lymphovascular emboli, and lymph node metastasis by a pathologist using the tumor proportion score (TPS). Results: We collected and analyzed surgical specimens from 36 patients with lung cancer with lymph node metastasis. In the primary tumor, 64% of cases were PD-L1 negative (TPS < 1%), 25% were PD-L1 low (TPS 1%–49%), and 11% were PD-L1 high (TPS ≥ 50%). In contrast, in lymphovascular tumor emboli, 89% of cases were PD-L1 negative, 11% were PD-L1 low, and none were PD-L1 high. In lymph node metastases, 72% of cases were PD-L1 negative, 17% were PD-L1 low, and 11% were PD-L1 high. Conclusions: We observed a significant decrease of PD-L1 expression in lymphovascular tumor emboli compared with that in primary tumors (p = 0.002). Whether such differences are related to intrinsic tumor cell heterogeneity or extrinsic factors such as the microenvironment warrants further investigation.