Combining Magnetic Resonance Imaging with Systemic Monocyte Evaluation for the Implementation of GBM Management

Int J Mol Sci. 2021 Apr 6;22(7):3797. doi: 10.3390/ijms22073797.

Abstract

Magnetic resonance imaging (MRI) is the gold standard for glioblastoma (GBM) patient evaluation. Additional non-invasive diagnostic modalities are needed. GBM is heavily infiltrated with tumor-associated macrophages (TAMs) that can be found in peripheral blood. FKBP51s supports alternative-macrophage polarization. Herein, we assessed FKBP51s expression in circulating monocytes from 14 GBM patients. The M2 monocyte phenotype was investigated by qPCR and flow cytometry using antibodies against PD-L1, CD163, FKBP51s, and CD14. MRI assessed morphologic features of the tumors that were aligned to flow cytometry data. PD-L1 expression on circulating monocytes correlated with MRI tumor necrosis score. A wider expansion in circulating CD163/monocytes was measured. These monocytes resulted in a dramatic decrease in patients with an MRI diagnosis of complete but not partial surgical removal of the tumor. Importantly, in patients with residual tumor, most of the peripheral monocytes that in the preoperative stage were CD163/FKBP51s- had turned into CD163/FKBP51s+. After Stupp therapy, CD163/FKBP51s+ monocytes were almost absent in a case of pseudoprogression, while two patients with stable or true disease progression showed sustained levels in such circulating monocytes. Our work provides preliminary but meaningful and novel results that deserve to be confirmed in a larger patient cohort, in support of potential usefulness in GBM monitoring of CD163/FKBP51s/CD14 immunophenotype in adjunct to MRI.

Keywords: FKBP51s; MRI; glioblastoma multiforme; liquid biopsy; pseudoprogression.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / blood
  • Antigens, Differentiation, Myelomonocytic / blood
  • B7-H1 Antigen / blood
  • Brain Neoplasms* / blood
  • Brain Neoplasms* / diagnostic imaging
  • Brain Neoplasms* / therapy
  • Female
  • Flow Cytometry*
  • Glioblastoma* / blood
  • Glioblastoma* / diagnostic imaging
  • Glioblastoma* / therapy
  • Humans
  • Lipopolysaccharide Receptors / blood
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Monocytes / metabolism*
  • Prospective Studies
  • Real-Time Polymerase Chain Reaction*
  • Receptors, Cell Surface / blood
  • Tacrolimus Binding Proteins / blood

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • B7-H1 Antigen
  • CD14 protein, human
  • CD163 antigen
  • CD274 protein, human
  • Lipopolysaccharide Receptors
  • Receptors, Cell Surface
  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 5