Expression of neuropilin-1 is linked to glioma associated microglia and macrophages and correlates with unfavorable prognosis in high grade gliomas

Abstract

High grade gliomas, including glioblastoma (GB), are devastating malignancies with very poor prognosis. Over the course of the last decade, there has been a failure to develop new treatments for GB. Reasons for this failure include the lack of validation of novel molecular targets, which are often characterized in animal models and directly transposed to human trials. Here we build on our previous findings, which describe how the multi-functional co-receptor Neuropilin-1 (NRP1) signals through glioma associated microglia/macrophages (GAMS) to promote murine glioma, and investigate NRP1 expression in human glioma. Clinical and gene expression data were obtained via The Cancer Genome Atlas (TCGA), and analyzed using R statistical software. Additionally, CIBERSORT in silico deconvolution was used to determine fractions of immune cell sub-populations within the gene expression datasets. We find that NRP1 expression is correlated with poor prognosis, glioma grade, and associates with the mesenchymal GB subtype. In human GB, NRP1 expression is highly correlated with markers of monocytes/macrophages, as well as genes that contribute to the pro-tumorigenic phenotype of these cells.

Targeting Tumor Associated Macrophages to Overcome Conventional Treatment Resistance in Glioblastoma

“…In high-grade gliomas, M2 macrophages were correlated with an unfavorable prognostic (Sørensen et al, 2018). Caponegro et al also described a correlation between the presence of TAMs and a poorest prognosis in GB (Caponegro et al, 2018). Furthermore, a study based on magnetic resonance imaging in GB showed that highly aggressive tumors were also correlated with the presence of TAMs (Zhou et al, 2018).…”

<p>Multiscale Selectivity and in vivo Biodistribution of NRP-1-Targeted Theranostic AGuIX Nanoparticles for PDT of Glioblastoma</p>

“…Positron emission tomography (PET) recordings were obtained with a camera dedicated to small animal studies (Inveon, Siemens Preclinical Solutions, Knoxville, USA). After rat anesthesia, 65 MBq of 18 F-FDG were injected as a bolus via a lateral tail vein cannulation. List-mode acquisitions of 120 min durations were initiated a few seconds prior to tracer injection, and the acquired PET data were subsequently reconstructed in 27 consecutive frames (ie, 5 frames of 120-s duration followed by 22 frames of 5-min duration) using the ordered-subsets expectation maximization 3D algorithm (OSEM3D, 4 iterations, 16 subsets, zoom 1) together with scatter and attenuation corrections based on transmission source measurement.…”

“…17 Moreover, NRP-1 has also been shown to function as a co-receptor for VEGF-R on glioma-associated macrophages (GAM) where it plays a key role in the accumulation of immunosuppressive and pro-angiogenic macrophages at sites of tumor hypoxia. 18 In the context of GBM and compared to standard therapeutic strategies, photodynamic therapy (PDT) appears to be an alternative or complementary approach that may reduce recurrence and improve the overall survival of patients. [19][20][21][22][23] Using an appropriate wavelength, the photodynamic process consists on the excitation of PS submit your manuscript | www.dovepress.com…”

Exploring Novel Molecular Targets for the Treatment of High-Grade Astrocytomas Using Peptide Therapeutics: An Overview

“…It was shown to be highly expressed in GBM cells and neo-vasculature, where it regulates glioma growth, progression, and recurrence. The expression of NRP-1 correlates with glioma grade and poor patient prognosis [80][81][82].…”