Dynamic changes in glioma macrophage populations after radiotherapy reveal CSF-1R inhibition as a strategy to overcome resistance.

Science Translational Medicine
Leila AkkariJohanna A Joyce

Abstract

Tumor-associated macrophages (TAMs) and microglia (MG) are potent regulators of glioma development and progression. However, the dynamic alterations of distinct TAM populations during the course of therapeutic intervention, response, and recurrence have not yet been fully explored. Here, we investigated how radiotherapy changes the relative abundance and phenotypes of brain-resident MG and peripherally recruited monocyte-derived macrophages (MDMs) in glioblastoma. We identified radiation-specific, stage-dependent MG and MDM gene expression signatures in murine gliomas and confirmed altered expression of several genes and proteins in recurrent human glioblastoma. We found that targeting these TAM populations using a colony-stimulating factor-1 receptor (CSF-1R) inhibitor combined with radiotherapy substantially enhanced survival in preclinical models. Our findings reveal the dynamics and plasticity of distinct macrophage populations in the irradiated tumor microenvironment, which has translational relevance for enhancing the efficacy of standard-of-care treatment in gliomas.

References

Jan 1, 1993·The Journal of Experimental Medicine·J L BaronC A Janeway
Feb 11, 2000·Brain Pathology·P Kubes, P A Ward
Mar 11, 2005·The New England Journal of Medicine·Roger StuppUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Aug 21, 2007·Glia·Luc GrandbarbePaul Heuschling
May 5, 2009·Translational Oncology·Dolores HambardzumyanEric C Holland
Jan 18, 2013·BMC Bioinformatics·Sonja HänzelmannJustin Guinney
Sep 24, 2013·Nature Medicine·Stephanie M PyonteckJohanna A Joyce
Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·John HallidayEric C Holland
May 9, 2014·Science·Ruth A FranklinMing O Li
Aug 19, 2014·Glia·Peter WieghoferMarco Prinz
Dec 4, 2014·Nature·Elisa Gomez PerdigueroHans-Reimer Rodewald
Dec 30, 2014·Trends in Cell Biology·Florian Klemm, Johanna A Joyce
Jan 22, 2015·Nucleic Acids Research·Matthew E RitchieGordon K Smyth
Apr 11, 2015·Cancer Cell·Brian Ruffell, Lisa M Coussens
Jun 25, 2015·Nature Reviews. Cancer·Holly E BarkerKevin J Harrington
Jul 1, 2015·Nature Reviews. Clinical Oncology·Dörthe Schaue, William H McBride
Jun 9, 2016·Nature Genetics·Jiguang WangRaul Rabadan
Jun 25, 2016·Nature Reviews. Cancer·Camilla EngblomMikael J Pittet
Nov 1, 2016·Nature Immunology·Anne ButtgereitMelanie Greter
Jan 17, 2017·Nature Neuroscience·Marco Prinz, Josef Priller
Feb 27, 2017·Cancer Research·Zhihong ChenDolores Hambardzumyan
Mar 22, 2018·Immunity·Max D Wellenstein, Karin E de Visser
Oct 18, 2018·Immunity·Martin GuilliamsSimon Yona
Oct 27, 2018·Nature Reviews. Drug Discovery·Luca Cassetta, Jeffrey W Pollard

❮ Previous
Next ❯

Citations

Jan 6, 2021·International Journal of Molecular Sciences·Alexander OuNazanin Majd
Nov 15, 2020·International Journal of Molecular Sciences·Daniel P Radin, Stella E Tsirka
Dec 31, 2020·Cells·Alessandra De LeoFilippo Veglia
Feb 19, 2021·Journal of Leukocyte Biology·Antoine FreuchetIgnacio Anegon
Mar 21, 2021·Seminars in Immunology·Mara De MartinoClaire Vanpouille-Box
Mar 26, 2021·Acta Neuropathologica Communications·Yona KimSun Ha Paek
Mar 23, 2021·Frontiers in Immunology·Darel Martínez BedoyaDenis Migliorini
Apr 4, 2021·Cancer Discovery·Leire BejaranoJohanna A Joyce
Mar 12, 2021·Nature Reviews. Neurology·Lily KeaneBertrand Joseph
May 1, 2021·Cells·Tyler J WildesCatherine T Flores
Jun 1, 2021·Frontiers in Immunology·Miranda W Yu, Daniela F Quail
Jun 8, 2021·Frontiers in Oncology·Mara De MartinoClaire Vanpouille-Box
Jun 8, 2021·Frontiers in Cell and Developmental Biology·Yanghong NiXuelei Ma
Jun 13, 2021·Nature Reviews. Clinical Oncology·Martina OttAmy B Heimberger
Jun 16, 2021·EMBO Molecular Medicine·Mara De MartinoLorenzo Galluzzi
Jul 21, 2021·Disease Models & Mechanisms·Woutje M BerdowskiTjakko J van Ham
Sep 30, 2021·Nature Reviews. Cancer·Brian M AndersenFrancisco J Quintana
Oct 14, 2021·Immunity·Katharina BorstMarco Prinz

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.