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

Cancer Immunol Immunother. 2021 Dec;70(12):3643-3650. doi: 10.1007/s00262-021-02951-2. Epub 2021 May 6.

Abstract

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.

Keywords: Glioma; Liquid biomarker; Longitudinal measurement; Soluble PD-L1; Systemic inflammation.

MeSH terms

  • Adult
  • Aged
  • B7-H1 Antigen / blood*
  • Bevacizumab / therapeutic use*
  • Biomarkers, Tumor / blood
  • Brain Neoplasms / blood
  • Brain Neoplasms / drug therapy
  • Female
  • Glioblastoma / blood
  • Glioblastoma / drug therapy
  • Glioma / blood*
  • Glioma / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / blood*
  • Neoplasm Recurrence, Local / drug therapy*
  • Young Adult

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Bevacizumab