Fibrotic response to anti-CSF-1R therapy potentiates glioblastoma recurrence.

Autor:	Watson SS; Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Center Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Centre, University Hospital Lausanne, 1011 Lausanne, Switzerland; Lundin Brain Tumour Centre, University Hospital Lausanne, 1011 Lausanne, Switzerland., Zomer A; Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Center Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Centre, University Hospital Lausanne, 1011 Lausanne, Switzerland., Fournier N; Agora Cancer Centre, University Hospital Lausanne, 1011 Lausanne, Switzerland; Translational Data Science Facility, SIB Swiss Institute of Bioinformatics, Agora Cancer Research Center Lausanne, 1011 Lausanne, Switzerland., Lourenco J; Agora Cancer Centre, University Hospital Lausanne, 1011 Lausanne, Switzerland; Translational Data Science Facility, SIB Swiss Institute of Bioinformatics, Agora Cancer Research Center Lausanne, 1011 Lausanne, Switzerland., Quadroni M; Proteomics Core Facility, University of Lausanne, 1011 Lausanne, Switzerland., Chryplewicz A; Agora Cancer Centre, University Hospital Lausanne, 1011 Lausanne, Switzerland; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland., Nassiri S; Agora Cancer Centre, University Hospital Lausanne, 1011 Lausanne, Switzerland; Translational Data Science Facility, SIB Swiss Institute of Bioinformatics, Agora Cancer Research Center Lausanne, 1011 Lausanne, Switzerland., Aubel P; Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Center Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Centre, University Hospital Lausanne, 1011 Lausanne, Switzerland; Lundin Brain Tumour Centre, University Hospital Lausanne, 1011 Lausanne, Switzerland., Avanthay S; Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Center Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Centre, University Hospital Lausanne, 1011 Lausanne, Switzerland., Croci D; Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Center Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Centre, University Hospital Lausanne, 1011 Lausanne, Switzerland., Abels E; Department of Neurosurgery, Department of Cell and Chemical Biology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands; Department of Neurosurgery, Haaglanden Medical Center, 2597 The Hague, the Netherlands., Broekman MLD; Department of Neurosurgery, Department of Cell and Chemical Biology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands; Department of Neurosurgery, Haaglanden Medical Center, 2597 The Hague, the Netherlands., Hanahan D; Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Center Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Centre, University Hospital Lausanne, 1011 Lausanne, Switzerland; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland; Swiss Cancer Center Leman (SCCL), Lausanne, Geneva, Switzerland., Huse JT; Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Daniel RT; Lundin Brain Tumour Centre, University Hospital Lausanne, 1011 Lausanne, Switzerland; Department of Neurosurgery, University Hospital of Lausanne, 1011 Lausanne, Switzerland., Hegi ME; Lundin Brain Tumour Centre, University Hospital Lausanne, 1011 Lausanne, Switzerland; Department of Clinical Neurosciences, University Hospital Lausanne, 1011 Lausanne, Switzerland., Homicsko K; Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Center Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Centre, University Hospital Lausanne, 1011 Lausanne, Switzerland; Department of Oncology, University Hospital of Lausanne, 1011 Lausanne, Switzerland., Cossu G; Lundin Brain Tumour Centre, University Hospital Lausanne, 1011 Lausanne, Switzerland; Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Hottinger AF; Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Center Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Centre, University Hospital Lausanne, 1011 Lausanne, Switzerland; Lundin Brain Tumour Centre, University Hospital Lausanne, 1011 Lausanne, Switzerland; Department of Oncology, University Hospital of Lausanne, 1011 Lausanne, Switzerland., Joyce JA; Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Center Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Centre, University Hospital Lausanne, 1011 Lausanne, Switzerland; Lundin Brain Tumour Centre, University Hospital Lausanne, 1011 Lausanne, Switzerland; Swiss Cancer Center Leman (SCCL), Lausanne, Geneva, Switzerland. Electronic address: johanna.joyce@unil.ch.
Jazyk:	angličtina
Zdroj:	Cancer cell [Cancer Cell] 2024 Sep 09; Vol. 42 (9), pp. 1507-1527.e11.
DOI:	10.1016/j.ccell.2024.08.012
Abstrakt:	Glioblastoma recurrence is currently inevitable despite extensive standard-of-care treatment. In preclinical studies, an alternative strategy of targeting tumor-associated macrophages and microglia through CSF-1R inhibition was previously found to regress established tumors and significantly increase overall survival. However, recurrences developed in ∼50% of mice in long-term studies, which were consistently associated with fibrotic scars. This fibrotic response is observed following multiple anti-glioma therapies in different preclinical models herein and in patient recurrence samples. Multi-omics analyses of the post-treatment tumor microenvironment identified fibrotic areas as pro-tumor survival niches that encapsulated surviving glioma cells, promoted dormancy, and inhibited immune surveillance. The fibrotic treatment response was mediated by perivascular-derived fibroblast-like cells via activation by transforming growth factor β (TGF-β) signaling and neuroinflammation. Concordantly, combinatorial inhibition of these pathways inhibited treatment-associated fibrosis, and significantly improved survival in preclinical trials of anti-colony-stimulating factor-1 receptor (CSF-1R) therapy. Competing Interests: Declaration of interests A.Z. is a current employee of Genmab; D.C. received consulting fees from Seed Biosciences S.A. and is a current employee of Novigenix; S.N. is a current employee of Roche Pharmaceuticals; A.F.H. has served on advisory boards and speaker’s bureau for Novocure and Bayer; M.E.H. has an advisory role at TME Pharma; J.A.J. received a speaker honorarium from Bristol Meyers Squibb, and served on the scientific advisory board of Pionyr Immunotherapeutics; J.A.J. and D.H. serve on the Cancer Cell editorial advisory board. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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