Protein expression of programmed cell death ligand 1 and ligand 2 and their prognostic values in extensive-stage small cell lung cancer.

Abstract

e20593 Background: The receptor-ligand interaction between programmed cell death protein-1 (PD-1) and its ligands (PD-L1 and PD-L2) plays a critical role in tumor immune evasion and has become a therapeutic target in a number of cancer types, including extensive stage small cell lung cancer (ES-SCLC). While there are some published data on PD-L1 expression in ES-SCLC, the results vary with different laboratory assays or thresholds of positivity employed. Data on PD-L2 expression is very limited in ES-SCLC. The prognostic values of these biomarkers are not well understood. The current study aims to address this data gap. Methods: A retrospective cohort study of patients with ES-SCLC receiving usual care in the clinical setting in Denmark was conducted. Formalin-fixed paraffin embedded (FFPE) tumor tissue samples and data on patient characteristics and clinical outcomes were obtained for the patient population. Protein expression of PD-L1 and PD-L2 was determined by immunohistochemistry (IHC), and a combined positive score (CPS, the percentage of tumor cells and mononuclear inflammatory cells expressing the biomarker at any intensity out of the total number of tumor cells) of ≥1 was used to define biomarker positivity. Kaplan-Meier plots and Cox proportional hazard models were employed to assess the relationship between PD-L1 and PD-L2 protein expression and overall survival (OS). Results: Among the 80 patients with ES-SCLC included in this study, 25 and 29 were positive for PD-L1 and PD-L2, respectively (Table). A total of 68 patients had concordant expression status of PD-L1 and PD-L2 (21 as double positive and 47 as double negative). There was a significant association between PD-L1 positivity and longer OS, which persisted after adjustment for age and stage at SCLC diagnosis, performance score, prior exposure to chemotherapy, and lactate dehydrogenase levels (Table). Similar results were observed for PD-L2 (Table), and the data did not suggest any additional prognostic value of PD-L2 expression independent of PD-L1 expression. Conclusions: PD-L1 and PD-L2 positivity was both observed, and highly correlated with each other, in approximately one third of the ES-SCLC tumor samples tested. Patients with PD-L1 or PD-L2 positive tumors have significantly longer OS than those with negative tumors in this study, independent of other known prognostic factors.[Table: see text]