Circulating PD-L1 levels change during bevacizumab-based treatment in recurrent glioma

• Published in: Cancer Immunology, Immunotherapy Vol. 70; no. 12; pp. 3643 - 3650
• Main Authors: Mair, Maximilian J., Ilhan-Mutlu, Ayseguel, Pajenda, Sahra, Kiesel, Barbara, Wöhrer, Adelheid, Widhalm, Georg, Dieckmann, Karin, Marosi, Christine, Wagner, Ludwig, Preusser, Matthias, Berghoff, Anna S.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2021; Springer Nature B.V
• Subjects: Adult; Aged; B7-H1 Antigen - blood; Bevacizumab; Bevacizumab - therapeutic use; Biomarkers, Tumor - blood; Brain cancer; Brain Neoplasms - blood; Brain Neoplasms - drug therapy; Brain tumors; C-reactive protein; Cancer Research; Central nervous system; Enzyme-linked immunosorbent assay; Female; Glioblastoma; Glioblastoma - blood; Glioblastoma - drug therapy; Glioma; Glioma - blood; Glioma - drug therapy; Humans; Immunology; Immunomodulation; Immunoregulation; Inflammation; Male; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; Neoplasm Recurrence, Local - blood; Neoplasm Recurrence, Local - drug therapy; Oncology; Original; Original Article; Patients; PD-L1 protein; Targeted cancer therapy; Young Adult; Soluble PD-L1; Longitudinal measurement; Glioma; Liquid biomarker; Systemic inflammation
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-021-02951-2

Purpose In primary brain tumors, the efficacy of immune-modulating therapies is still under investigation as inflammatory responses are restricted by tight immunoregulatory mechanisms in the central nervous system. Here, we measured soluble PD-L1 (sPD-L1) in the plasma of patients with recurrent glioblastoma (GBM) and recurrent WHO grade II–III glioma treated with bevacizumab-based salvage therapy. Methods Thirty patients with recurrent GBM and 10 patients with recurrent WHO grade II–III glioma were treated with bevacizumab-based salvage therapy at the Medical University of Vienna. Prior to each treatment cycle, EDTA plasma was drawn and sPD-L1 was measured applying a sandwich ELISA with a lower detection limit of 0.050 ng/ml. Leukocyte counts and C-reactive protein (CRP) levels were measured according to institutional practice. Results Median number of sPD-L1 measurements was 6 per patient (range: 2–24). At baseline, no significant difference in sPD-L1 concentrations was observed between WHO grade II–III glioma and GBM. Intra-patient variability of sPD-L1 concentrations was significantly higher in WHO grade II–III glioma than in GBM ( p  = 0.014) and tendentially higher in IDH-mutant than in IDH-wildtype glioma ( p  = 0.149) In WHO grade II–III glioma, sPD-L1 levels were significantly lower after one administration of bevacizumab than at baseline (median: 0.039 ng/ml vs. 0.4855 ng/ml, p  = 0.036). In contrast, no significant change could be observed in patients with GBM. Conclusions Changes in systemic inflammation markers including sPD-L1 are observable in patients with recurrent glioma under bevacizumab-based treatment and differ between WHO grade II–III glioma and GBM.