Intra- and Intertumoral Microglia/Macrophage Infiltration and Their Associated Molecular Signature Is Highly Variable in Canine Oligodendroglioma: A Preliminary Evaluation.

Autor: Toedebusch RG; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA., Wei NW; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA., Simafranca KT; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA., Furth-Jacobus JA; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA., Brust-Mascher I; Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA., Stewart SL; Division of Biostatistics, School of Medicine, University of California, Davis, CA 95616, USA.; UC Davis Comprehensive Cancer Center, Sacramento, CA 95817, USA., Dickinson PJ; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.; UC Davis Comprehensive Cancer Center, Sacramento, CA 95817, USA., Woolard KD; Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA., Li CF; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA., Vernau KM; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA., Meyers FJ; UC Davis Comprehensive Cancer Center, Sacramento, CA 95817, USA.; Department of Internal Medicine, Division of Hematology and Oncology, Center for Precision Medicine, Microbiology, and Immunology, School of Medicine, University of California, Sacramento, CA 95817, USA., Toedebusch CM; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.; UC Davis Comprehensive Cancer Center, Sacramento, CA 95817, USA.
Jazyk: angličtina
Zdroj: Veterinary sciences [Vet Sci] 2023 Jun 19; Vol. 10 (6). Date of Electronic Publication: 2023 Jun 19.
DOI: 10.3390/vetsci10060403
Abstrakt: The goal of this study was to define the glioma-associated microglia/macrophage (GAM) response and associated molecular landscape in canine oligodendrogliomas. Here, we quantified the intratumoral GAM density of low- and high-grade oligodendrogliomas compared to that of a normal brain, as well as the intratumoral concentration of several known GAM-derived pro-tumorigenic molecules in high-grade oligodendrogliomas compared to that in a normal brain. Our analysis demonstrated marked intra- and intertumoral heterogeneity of GAM infiltration. Correspondingly, we observed significant variability in the intratumoral concentrations of several GAM-associated molecules, unlike what we previously observed in high-grade astrocytomas. However, high-grade oligodendroglioma tumor homogenates (n = 6) exhibited an increase in the pro-tumorigenic molecules hepatocyte growth factor receptor (HGFR) and vascular endothelial growth factor (VEGF), as we observed in high-grade astrocytomas. Moreover, neoplastic oligodendrocytes displayed robust expression of GAL-3, a chimeric galectin implicated in driving immunosuppression in human glioblastoma. While this work identifies shared putative therapeutic targets across canine glioma subtypes (HGFR, GAL-3), it highlights several key differences in the immune landscape. Therefore, a continued effort to develop a comprehensive understanding of the immune microenvironment within each subtype is necessary to inform therapeutic strategies going forward.
Databáze: MEDLINE