Spatial analysis of the metastatic brain tumor immune and extracellular matrix microenvironment

Metastatic cancer is responsible for the overwhelming majority of cancer-related deaths, with metastatic tumors being the most common neoplasms affecting the central nervous system. One of the major factors regulating tumor biology is the tumor microenvironment. However, little is known about the ce...

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Main Authors: Samuel S. Widodo, Marija Dinevska, Lucero Cuzcano, Michael Papanicolaou, Thomas R. Cox, Stanley S. Stylli, Theo Mantamadiotis
Format: Article
Language:English
Published: Elsevier 2023-07-01
Series:Advances in Cancer Biology - Metastasis
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2667394023000102
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author Samuel S. Widodo
Marija Dinevska
Lucero Cuzcano
Michael Papanicolaou
Thomas R. Cox
Stanley S. Stylli
Theo Mantamadiotis
author_facet Samuel S. Widodo
Marija Dinevska
Lucero Cuzcano
Michael Papanicolaou
Thomas R. Cox
Stanley S. Stylli
Theo Mantamadiotis
author_sort Samuel S. Widodo
collection DOAJ
description Metastatic cancer is responsible for the overwhelming majority of cancer-related deaths, with metastatic tumors being the most common neoplasms affecting the central nervous system. One of the major factors regulating tumor biology is the tumor microenvironment. However, little is known about the cellular and non-cellular composition of metastatic brain tumors and how tumor cell ontogeny influences the metastatic brain tumor microenvironment. By integrating multiplex immunohistochemistry and histopathological analysis to investigate composition and the spatial relationship between neoplastic cells, infiltrating and brain resident immune cells and the extracellular matrix, we demonstrate that metastatic brain tumors exhibit differences in extracellular matrix deposition, compared with the most common primary brain tumor type, glioblastoma, and that the dominant immune cell types in metastatic brain tumors are immunosuppressive macrophages, which preferentially localize to extracellular matrix-rich stromal regions.
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spelling doaj.art-b2b6fab43f1a48828905a3e7969b560a2023-06-20T04:21:29ZengElsevierAdvances in Cancer Biology - Metastasis2667-39402023-07-017100096Spatial analysis of the metastatic brain tumor immune and extracellular matrix microenvironmentSamuel S. Widodo0Marija Dinevska1Lucero Cuzcano2Michael Papanicolaou3Thomas R. Cox4Stanley S. Stylli5Theo Mantamadiotis6Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, AustraliaDepartment of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, AustraliaDepartment of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, AustraliaThe Garvan Institute of Medical Research and the Kinghorn Cancer Centre, Cancer Ecosystems Program, Sydney, NSW, Australia; School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, AustraliaThe Garvan Institute of Medical Research and the Kinghorn Cancer Centre, Cancer Ecosystems Program, Sydney, NSW, Australia; School of Clinical Medicine, St Vincent's Healthcare Clinical Campus, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, AustraliaDepartment of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia; Department of Neurosurgery, Royal Melbourne Hospital, Parkville, VIC, AustraliaDepartment of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia; Department of Microbiology and Immunology, The University of Melbourne, Melbourne, VIC, Australia; Centre for Stem Cell Systems, The University of Melbourne, Parkville, VIC, Australia; Corresponding author. Department of Microbiology and Immunology, The University of Melbourne, VIC, Australia.Metastatic cancer is responsible for the overwhelming majority of cancer-related deaths, with metastatic tumors being the most common neoplasms affecting the central nervous system. One of the major factors regulating tumor biology is the tumor microenvironment. However, little is known about the cellular and non-cellular composition of metastatic brain tumors and how tumor cell ontogeny influences the metastatic brain tumor microenvironment. By integrating multiplex immunohistochemistry and histopathological analysis to investigate composition and the spatial relationship between neoplastic cells, infiltrating and brain resident immune cells and the extracellular matrix, we demonstrate that metastatic brain tumors exhibit differences in extracellular matrix deposition, compared with the most common primary brain tumor type, glioblastoma, and that the dominant immune cell types in metastatic brain tumors are immunosuppressive macrophages, which preferentially localize to extracellular matrix-rich stromal regions.http://www.sciencedirect.com/science/article/pii/S2667394023000102Brain cancerMetastatic brain cancerTumor microenvironmentMacrophagesT-cellsExtracellular matrix
spellingShingle Samuel S. Widodo
Marija Dinevska
Lucero Cuzcano
Michael Papanicolaou
Thomas R. Cox
Stanley S. Stylli
Theo Mantamadiotis
Spatial analysis of the metastatic brain tumor immune and extracellular matrix microenvironment
Advances in Cancer Biology - Metastasis
Brain cancer
Metastatic brain cancer
Tumor microenvironment
Macrophages
T-cells
Extracellular matrix
title Spatial analysis of the metastatic brain tumor immune and extracellular matrix microenvironment
title_full Spatial analysis of the metastatic brain tumor immune and extracellular matrix microenvironment
title_fullStr Spatial analysis of the metastatic brain tumor immune and extracellular matrix microenvironment
title_full_unstemmed Spatial analysis of the metastatic brain tumor immune and extracellular matrix microenvironment
title_short Spatial analysis of the metastatic brain tumor immune and extracellular matrix microenvironment
title_sort spatial analysis of the metastatic brain tumor immune and extracellular matrix microenvironment
topic Brain cancer
Metastatic brain cancer
Tumor microenvironment
Macrophages
T-cells
Extracellular matrix
url http://www.sciencedirect.com/science/article/pii/S2667394023000102
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