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ARTICLE

Microglia and brain macrophages are differentially associated with tumor necrosis in glioblastoma: A link to tumor progression

CHRISTINA LOH1, YUQI ZHENG1, ISLAM ALZOUBI2, KIMBERLEY L. ALEXANDER3,4, MAGGIE LEE4, WEI-DONG CAI2, YANG SONG5, KERRIE MCDONALD6, ANNA K. NOWAK7, RICHARD B. BANATI8,9, MANUEL B. GRAEBER1,4,10,*
1 Ken Parker Brain Tumor Research Laboratories, Brain and Mind Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2050, Australia
2 School of Computer Science, The University of Sydney, Sydney, NSW 2008, Australia
3 Neurosurgery Department, Chris O’Brien Lifehouse, Camperdown, NSW 2050, Australia
4 Department of Neuropathology, Royal Prince Alfred Hospital and Brain and Mind Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia
5 School of Computer Science and Engineering, University of New South Wales, Sydney, NSW 2052, Australia
6 Brain Cancer Consultancy, Sydney, NSW 2040, Australia
7 Medical School, University of Western Australia, Crawley Campus, Perth, WA 6009, Australia
8 Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2050, Australia
9 Santuario Accademico S. Giovanni D’Andorno, Casa Alpina ‘Principessa Laetitia’, Frazione Bele, Campiglia Cervo, 13812, Italy
10 University of Sydney Association of Professors (USAP), University of Sydney, Sydney, NSW 2006, Australia
* Corresponding Author: MANUEL B. GRAEBER. Email: email

Oncology Research https://doi.org/10.32604/or.2024.056436

Received 23 July 2024; Accepted 12 November 2024; Published online 27 November 2024

Abstract

Background: Microglia and brain macrophages contribute significantly to the tumor microenvironment in highly malignant glioblastoma where they are considered important drivers of tumor progression. A better understanding of the role of the brain macrophages present in glioblastoma appears crucial for improving therapeutic outcomes, especially in the context of novel immunotherapeutic approaches. Methods: We investigated the regulation of two well-established markers for microglia and brain macrophages, IBA1 and CD163, in relation to glioblastoma tumor necrosis using immunohistochemistry and modality fusion heatmaps of whole slide images obtained from adjacent tissue sections. Results: IBA1 and CD163 showed remarkable differences in relation to glioblastoma tumor necrosis. Generally, IBA1 immunoreactive cells were far less common in necrotic tissue areas than CD163-expressing cells. We also found extensive and frequently diffuse extracellular CD163 deposition, especially in hypocellular necrobiotic tumor regions where IBA1 was typically absent. Conclusions: Resident microglia seem more likely to be important for the diffuse infiltration of glioma cells in hypercellular tissue areas, whereas myeloid macrophages may be the main macrophage population in the wake of tumor necrosis. Since the necrotic niche with its interactions between microglia, brain macrophages, and glioblastoma/glioma stem cells is increasingly recognised as an important factor in tumor progression, further detailed studies of the macrophage populations in glioblastoma are warranted.

Keywords

Bone marrow-derived macrophages (BMDM); CD163; Glioblastoma/glioma stem cells (GSCs); IBA1; Microglia; Multimodal whole slide analysis; Tumor microenvironment

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