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

Quintino Giorgio D’Alessandris,Maria Fiammetta Romano,Martina Tufano,Giuseppe Maria Della Pepa,Simone Cottonaro,Mario Balducci,Giovanni Sabatino,Carolina Giordano,Marco Gessi,Alessandro Olivi,Simona Romano,Simona Gaudino,Cesare Colosimo

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.

Highlights

Glioblastoma (GBM) is the most common malignant primary brain tumor, accounting for 54% of all gliomas and 16% of all primary brain tumors [1]
Patients contain an expansion of M2 monocytes, which can be used for diagnostic purposes, we measured the levels of ARG1, MSR1, MRC1, and TBRII by qPCR
FKBP51 is an event that concurs with the acquisition of M2 features, namely, IL-10, STAT-3, and PD-L1 upregulation [21]

Summary

Introduction

Glioblastoma (GBM) is the most common malignant primary brain tumor, accounting for 54% of all gliomas and 16% of all primary brain tumors [1]. Despite advances in treatment modalities, GBM remains an incurable tumor with an average survival of fewer than two years. Standard treatment consists of maximal surgical resection followed by radio-chemotherapy according to Stupp protocol [2]. Surgical resection is a critical step because the invasive tumor cells that remain after surgery and survive the treatments are likely responsible for tumor recurrence [3]. Magnetic resonance imaging (MRI) remains the reference standard for the pre-operative, post-operative, and follow-up evaluation of glioma patients [4]. Post-operative and follow-up MRI assess the extent of surgical resection and treatment response. GBM is known to have a strong tendency to relapse after surgery and radio/chemotherapy treatments. At the time of relapse, the median survival is only 5–7 months despite therapy [5]

Methods

Results

Conclusion