Insights into CSF-1R Expression in the Tumor Microenvironment

The colony-stimulating factor 1 receptor (CSF-1R) plays a pivotal role in orchestrating cellular interactions within the tumor microenvironment (TME). Although the CSF-1R has been extensively studied in myeloid cells, the expression of this receptor and its emerging role in other cell types in the T...

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Main Authors: Caterina Tomassetti, Gaia Insinga, Francesca Gimigliano, Andrea Morrione, Antonio Giordano, Emanuele Giurisato
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/12/10/2381
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author Caterina Tomassetti
Gaia Insinga
Francesca Gimigliano
Andrea Morrione
Antonio Giordano
Emanuele Giurisato
author_facet Caterina Tomassetti
Gaia Insinga
Francesca Gimigliano
Andrea Morrione
Antonio Giordano
Emanuele Giurisato
author_sort Caterina Tomassetti
collection DOAJ
description The colony-stimulating factor 1 receptor (CSF-1R) plays a pivotal role in orchestrating cellular interactions within the tumor microenvironment (TME). Although the CSF-1R has been extensively studied in myeloid cells, the expression of this receptor and its emerging role in other cell types in the TME need to be further analyzed. This review explores the multifaceted functions of the CSF-1R across various TME cellular populations, including tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs), cancer-associated fibroblasts (CAFs), endothelial cells (ECs), and cancer stem cells (CSCs). The activation of the CSF-1R by its ligands, colony-stimulating factor 1 (CSF-1) and Interleukin-34 (IL-34), regulates TAM polarization towards an immunosuppressive M2 phenotype, promoting tumor progression and immune evasion. Similarly, CSF-1R signaling influences MDSCs to exert immunosuppressive functions, hindering anti-tumor immunity. In DCs, the CSF-1R alters antigen-presenting capabilities, compromising immune surveillance against cancer cells. CSF-1R expression in CAFs and ECs regulates immune modulation, angiogenesis, and immune cell trafficking within the TME, fostering a pro-tumorigenic milieu. Notably, the CSF-1R in CSCs contributes to tumor aggressiveness and therapeutic resistance through interactions with TAMs and the modulation of stemness features. Understanding the diverse roles of the CSF-1R in the TME underscores its potential as a therapeutic target for cancer treatment, aiming at disrupting pro-tumorigenic cellular crosstalk and enhancing anti-tumor immune responses.
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spelling doaj-art-e6cb7bb6e9334cbc9f48bedb046f596a2025-08-20T02:11:04ZengMDPI AGBiomedicines2227-90592024-10-011210238110.3390/biomedicines12102381Insights into CSF-1R Expression in the Tumor MicroenvironmentCaterina Tomassetti0Gaia Insinga1Francesca Gimigliano2Andrea Morrione3Antonio Giordano4Emanuele Giurisato5Department of Biotechnology Chemistry and Pharmacy, University of Siena, 53100 Siena, ItalyDepartment of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, 80138 Napoli, ItalyDepartment of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, 80138 Napoli, ItalySbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USADepartment of Medical Biotechnologies, University of Siena, 53100 Siena, ItalyDepartment of Biotechnology Chemistry and Pharmacy, University of Siena, 53100 Siena, ItalyThe colony-stimulating factor 1 receptor (CSF-1R) plays a pivotal role in orchestrating cellular interactions within the tumor microenvironment (TME). Although the CSF-1R has been extensively studied in myeloid cells, the expression of this receptor and its emerging role in other cell types in the TME need to be further analyzed. This review explores the multifaceted functions of the CSF-1R across various TME cellular populations, including tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs), cancer-associated fibroblasts (CAFs), endothelial cells (ECs), and cancer stem cells (CSCs). The activation of the CSF-1R by its ligands, colony-stimulating factor 1 (CSF-1) and Interleukin-34 (IL-34), regulates TAM polarization towards an immunosuppressive M2 phenotype, promoting tumor progression and immune evasion. Similarly, CSF-1R signaling influences MDSCs to exert immunosuppressive functions, hindering anti-tumor immunity. In DCs, the CSF-1R alters antigen-presenting capabilities, compromising immune surveillance against cancer cells. CSF-1R expression in CAFs and ECs regulates immune modulation, angiogenesis, and immune cell trafficking within the TME, fostering a pro-tumorigenic milieu. Notably, the CSF-1R in CSCs contributes to tumor aggressiveness and therapeutic resistance through interactions with TAMs and the modulation of stemness features. Understanding the diverse roles of the CSF-1R in the TME underscores its potential as a therapeutic target for cancer treatment, aiming at disrupting pro-tumorigenic cellular crosstalk and enhancing anti-tumor immune responses.https://www.mdpi.com/2227-9059/12/10/2381CSF-1Rtumor microenvironmentCAFsECsTAMsMDSCs
spellingShingle Caterina Tomassetti
Gaia Insinga
Francesca Gimigliano
Andrea Morrione
Antonio Giordano
Emanuele Giurisato
Insights into CSF-1R Expression in the Tumor Microenvironment
Biomedicines
CSF-1R
tumor microenvironment
CAFs
ECs
TAMs
MDSCs
title Insights into CSF-1R Expression in the Tumor Microenvironment
title_full Insights into CSF-1R Expression in the Tumor Microenvironment
title_fullStr Insights into CSF-1R Expression in the Tumor Microenvironment
title_full_unstemmed Insights into CSF-1R Expression in the Tumor Microenvironment
title_short Insights into CSF-1R Expression in the Tumor Microenvironment
title_sort insights into csf 1r expression in the tumor microenvironment
topic CSF-1R
tumor microenvironment
CAFs
ECs
TAMs
MDSCs
url https://www.mdpi.com/2227-9059/12/10/2381
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AT gaiainsinga insightsintocsf1rexpressioninthetumormicroenvironment
AT francescagimigliano insightsintocsf1rexpressioninthetumormicroenvironment
AT andreamorrione insightsintocsf1rexpressioninthetumormicroenvironment
AT antoniogiordano insightsintocsf1rexpressioninthetumormicroenvironment
AT emanuelegiurisato insightsintocsf1rexpressioninthetumormicroenvironment