The Change of Soluble Programmed Cell Death Ligand-1 (sPD-L1) in Patients with Glioma during Radiotherapy and Impact on Clinical Outcome

Abstract

It has been proven that the levels of soluble programmed death-ligand 1 (sPD-L1) are associated with prognosis in extracranial malignancies. Nevertheless, due to the blood-brain barrier (BBB) the expression of sPD-L1 in patients with glioma is still unknown. The purpose of this study is to evaluate plasma concentrations of sPD-L1 before and after radiotherapy (RT) for patients with glioma, and investigate its relationships with clinical outcome. Between October 2017 and September 2018, glioma patients treated with RT were enrolled. Blood samples were collected before and after RT (30 ± 10 Gy, 2 Gy/f). We quantified the sPD-L1 levels using enzyme-linked immunosorbent assay (ELISA) kits. The isocitrate dehydrogenase-1 (IDH-1) promoter status and the expression of Ki-67 were also evaluated by immunohistochemistry (IHC). The associations between sPD-L1 level and the clinical features were assessed with Pearson or Spearman correlation. The progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier method. Sixty glioma patients were included, with the median age 52-year-old (range, 18 – 75 years). The proportion of grade I, II, III, IV were 6.7%, 25.0%, 26.7% and 41.6%, respectively. The sPD-L1 levels before RT were significantly associated with tumor grade (r = 0.495, P < 0.001), IDH-1 promoter status (r = 0.379, P = 0.016) and Ki-67 expression rate (r = 0.434, P = 0.003). Using 14.35 pg/mL as the cutoff, statistically significant worse PFS and OS were both noted in patients with higher sPD-L1 level before RT than those with lower ones (20.4 vs. 26.7 months, 23.1 vs. 28.7 months, P = 0.027, 0.008, respectively). Comparing with that before RT, the mean level of sPD-L1 significantly increased after RT (41.14 ± 52.41 vs. 52.49 ± 61.84 pg/ml, P = 0.011). sPD-L1 was increased in 31 patients, in contrast, that was reduced in 20 patients. Further analysis showed that the patients with decreased sPD-L1 had significantly worse OS (20.8% vs 29.5%, P = 0.040) than increased ones. The increased level of sPD-L1 in IDH-1 mutation patients was higher than that in wide-type ones. To the best of our known, this is the first study reported that PD-L1 can be assayed in peripheral blood of glioma patients. The reason might be that BBB is destroyed. sPD-L1 might be a potential biomarker to predict the outcome in glioma. The elevated level of sPD-L1 after RT suggests that the strategy of combination with immune checkpoint inhibitors and RT is promising for glioma, especially for patients with IDH-1 mutation.