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

Abstract

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background: </jats:bold>It has been proved that the levels of soluble programmed death-ligand 1 (sPD-L1) are associated with prognosis in extracranial malignancies. However, the expression of sPD-L1 in glioma patients receiving radiotherapy (RT) still remains unclear.The purpose of this study is to evaluate the concentration of sPD-L1in the plasma of glioma patients before and after RT, and to explore its relationship with clinical outcomes.<jats:bold>Methods: </jats:bold>Between October 2017 and September 2018, the glioma patients treated with RT (30 ± 10 Gy, 2 Gy/f) were enrolled and the blood samples were collected before and after RT. We quantified the sPD-L1 levels by enzyme-linked immunosorbent assay (ELISA). The isocitrate dehydrogenase-1 (IDH-1) promoter status and Ki-67 expression were evaluated by immunohistochemistry. The murine models of glioma were used to address whether circulating sPD-L1 molecules are directly targeted by the anti-PD-L1 antibody. The associations between sPD-L1 and clinical features were assessed with Pearson or Spearman correlation. The progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier method.<jats:bold>Results: </jats:bold>Sixty glioma patients were included, with the median age 52-year-old. The proportion of grade I, II, III, IV were 6.7%, 23.3%, 28.4% and 41.6%, respectively. The baseline sPD-L1 levels were significantly associated with tumor grades, IDH-1 mutation status and Ki-67 expression. Using 14.35 pg/mL as the cutoff, significantly worse PFS and OS were both observed in patients with higher baseline level of sPD-L1 (<jats:italic>P</jats:italic> = 0.027, 0.008, respectively). RT significantly increased the mean level of sPD-L1 (<jats:italic>P</jats:italic> &lt; 0.001). Further analysis showed that increased level of sPD-L1 in IDH-1 mutation patients was higher than that in wide-type ones. Furthermore, the murine models of glioma indicate that sPD-L1 can be blocked by anti-PD-L1 antibody. <jats:bold>Conclusion: </jats:bold>This study reported that sPD-L1 might be a potential biomarker to predict the outcome in glioma receiving RT. The elevated level of sPD-L1 after RT suggested that the strategy of combination with immune checkpoint inhibitors and RT might be promising for glioma, especially for patients with IDH-1 mutation.</jats:p>

The Change of Soluble Programmed Cell Death-Ligand 1 in Glioma Patients Receiving Radiotherapy and Its Impact on Clinical Outcomes

“…We thank the patients who participated in this study, their families, and the staff members at the study sites who cared for them. This manuscript has been released as a pre-print at Research Square (35).…”