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

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.

Systemic Immune Dysregulation in Early Breast Cancer Is Associated With Decreased Plasma Levels of Both Soluble Co-Inhibitory and Co-Stimulatory Immune Checkpoint Molecules

“…In this setting the numbers of these circulating M2-like monocytes are not only significantly increased relative to those of healthy control subjects and patients with benign disease ( 49 , 50 ), but are also metabolically quiescent, displaying transcriptomes on activation that reflect decreased expression of gene sets involved in oxidative phosphorylation, fatty acid metabolism, and inner mitochondrial membrane protein complex ( 49 ). A similar association between an intra-tumoral and systemic predominance of M2-like macrophages/monocytes associated with a poor prognosis has also been described in glioma/glioblastoma patients ( 51 , 52 ).…”

[Retracted] To Investigate the Effect of Magnetic Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) in the Diagnosis of Mild Craniocerebral Injury

“…Giordano et al found that DTI imaging technology has characteristics of brain endoplasmic injury in toxic encephalopathy. Compared with the control group, FA in the corpus callosum and corpus callosum decreased significantly [ 13 ].…”

Strategies, considerations, and recent advancements in the development of liquid biopsy for glioblastoma: a step towards individualized medicine in glioblastoma

“…Importantly, Giordano et al demonstrated that there is an increase in CD163+ monocytes in GBM patients compared with healthy donors, which become CD163/FKBP51s+ in cases of residual tumor. 71 Furthermore, CD163/FKBP51s+ monocytes were significantly decreased in individuals with pseudoprogression compared with those with true progression. Similar to monocytes, platelets also infiltrate the tumor microenvironment and are capable of providing angiogenic factors for GBM growth.…”

“…70 GBM itself is enriched in monocytes, which differentiate into myeloidderived suppressor cells, nonclassical monocytes, and M2 macrophages. 70,71 These cells can then reenter circulation to exert their global immunosuppressive effects. Importantly, Giordano et al demonstrated that there is an increase in CD163+ monocytes in GBM patients compared with healthy donors, which become CD163/FKBP51s+ in cases of residual tumor.…”