P2.04-85 Clinical Significance of the PD-L2 Expression in Patients with NSCLC Receiving Anti-PD-1 Inhibitors

The programmed cell death 1 (PD-1) receptor–ligand interaction is a major pathway often hijacked by tumors to suppress immune control. Programmed cell death-ligand 1 (PD-L1), a ligand of PD-1, can potentially predict the response to anti-PD-1/PD-L1 inhibitors in patients with non-small cell lung cancer (NSCLC); however, the role of PD-L2, another ligand of PD-1, remains unclear in patients receiving anti-PD-1 inhibitors. This retrospective study aims to determine the significance of the PD-L2 expression in anti-PD-1 inhibitors–treated patients with NSCLC. We enrolled 82 patients with advanced or recurrent NSCLC who received anti-PD-1 inhibitors. The PD-L2 expression was assessed by immunohistochemical analysis staining with an antibody of PD-L2 (1:200, clone 176611), and cases with >1% tumor staining of PD-L2 were considered positive. Furthermore, we analyzed correlations between PD-L2 expression and patients’ characteristics, efficacy, and immune-related adverse events (irAEs) of anti-PD-1 inhibitors. In this study, 59 (72.0%) and 56 (68.3) patients with NSCLC exhibited positive tumor PD-L2 and PD-L1 staining, respectively. Overall, 39 irAEs developed in 36 patients. The PD-L2 expression markedly correlated with the development of irAEs; however, we observed no correlation between PD-L2 expression and the efficacy of anti-PD-1 inhibitors. Other factors, including the PD-L1 expression, age, sex, smoking status, histology, did not correlate with the development of irAEs. This study suggests that the PD-L2 expression could be accountable for the development of irAEs in anti-PD-1 inhibitors–treated patients with NSCLC.