Soluble Programmed Death-Ligand 1 (sPD-L1) as a Novel Biomarker for the Combination of Anti-PD-L1 Antibody and Radiotherapy for Glioma Patients

Abstract

In our previous study, it has been proven that high level of soluble programmed death-ligand 1 (sPD-L1) is considered a predictor of negative clinical outcomes in glioma. However, the expression of sPD-L1 can change dynamically during radiotherapy (RT), and the effect of sPD-L1 has not been thoroughly elucidated. The purpose of this study was to uncover the dynamics of circulating sPD-L1 levels in glioma patients undergoing RT and to investigate the significance of plasma sPD-L1 levels as a biomarker for combining anti-PD-L1 antibody and RT.Glioma patients treated with RT between October 2019 and September 2020 were prospectively recruited and sPD-L1 levels were measured using enzyme-linked immunosorbent assay (ELISA). Blood samples were obtained before RT (0f), during RT (15 ± 2f) and RT end (30 ± 2f). Flow cytometry were used to address whether circulating sPD-L1 molecules can affect the CD8+ T cells activation and function in the adaptive immune response. Glioma murine model were used to validate whether combine RT and anti-PD-L1 antibody can be a promising therapeutic strategy in gliomas.Thirty-two GBM patients treated with RT were included. The proportions of grade I, II, III, and IV gliomas were 6.2%, 28.1%, 21.9%, and 43.8%. RT significantly increased the mean level of sPD-L1 (0f vs. 15 ± 2f: 55.7 ± 19.2 vs.76.7 ± 38.8, P = 0.008; 0f vs. 30 ± 2f: 55.7 ± 19.2 vs.80.94 ± 44.9, P = 0.005). However, there was no significantly difference between during RT (15 ± 2f) and RT end (30 ± 2f). We performed the CD8+ T cells suppression analysis using mice plasma in vitro. The plasma from mice after anti-PD-L1 treatment (the concentration of sPD-L1 could not be detected) didn't show any suppression activity. Instead, the plasma from the mice without anti-PDL1 treatment exhibited the remarkable CD8+ T cell suppression capacity. These results indicated that the sPD-L1 can play an important role in T cell suppression. Furthermore, the glioma murine model indicated that the combination of irradiate (IR) and anti-PD-L1 significantly reduced tumor growth than either IR or anti-PD-L1 antibody monotherapy (anti-PD-L1 vs. IR plus anti-PD-L1: 789.67 ± 55.86 mm3vs. 292.16 ± 102.98 mm3 on day 31, P < 0.001; IR vs. IR plus anti-PD-L1: 697.02 ± 12.98 mm3vs. 292.16 ± 102.98 mm3 on day 31, P < 0.001).This study reported that sPD-L1 might be a potential biomarker in glioma patients receiving RT. This finding means that compensation for the potential sequestration of antibodies needs to be considered in the optimization of PD-L1 blockade therapies. Because not all administered anti-PD-L1 immunotherapeutic antibodies may reach the surface of tumor cells, with a potentially appreciable proportion being sequestered by sPD-L1 within the circulation. The elevated level of sPD-L1 after RT suggested that the strategy of a combination of immune checkpoint inhibitors and RT might be promising for glioma patients.X. Ding: None. Z. Zhou: None. Z. Ge: None. Y. Guo: None. Y. Chen: None. S. Nie: None. J. Yu: None. M. Hu: None.