Cited by 183Immune cells in cancerImmunotherapy and Immune ResponsesPhagocytosis and Immune Regulation

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Functional plasticity of macrophages: in situ reprogramming of tumor-associated macrophages

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Stout, Robert D, Watkins, Stephanie K, Suttles, Jill·2009·Journal of Leukocyte Biology

DOI 10.1189/jlb.0209073PMC PMC2774875

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Abstract

Functionally polarized macrophages in chronic pathologies are highly adaptable cells displaying a functional response to tissue signals, which response can be reprogrammed to therapeutic advantage. The extent to which the functional heterogeneity of Mφs is dependent on the differentiation of functional sublineages remains unresolved. One alternative hypothesis proposes that Mφs are functionally plastic cells, which are capable of altering their functional activities progressively in response to progressively changing signaling molecules generated in their microenvironment. This “functional plasticity” hypothesis predicts that the functionally polarized Mφs in chronic pathologies do not represent Mφ sublineages but rather, are mutable phenotypes sustained by chronic signaling from the pathological environment. Solid TAMφs are chronically polarized to provide activities that support tumor growth and metastasis and suppress adaptive immune responses. In support of the functional plasticity hypothesis, administration of slow-release microsphere-encapsulated IL-12 successfully reprogrammed TAMφs in situ, reducing Mφ support of tumor growth and metastasis and enhancing Mφ proimmunogenic activities. Increased knowledge of how Mφ function is regulated and how polarized Mφs can be reprogrammed in situ will increase our ability to control Mφ function in a variety of pathological states, including cancer and chronic inflammatory disease.

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Authors: Stout, R. D., Watkins, S. K., & Suttles, J.
Affiliations: University of Louisville (US)
Frederick National Laboratory for Cancer Research (US)
Corresponding author: Stout, Robert D
ORCID: Watkins, Stephanie K
Venue: Journal of Leukocyte Biology
Publisher: Oxford University Press (OUP)
Published: 2009-07-15
Volume: 86
Issue: 5
Pages: 1105-1109
ISSN: 0741-5400 (ISSN-L)
1938-3673
DOI: 10.1189/jlb.0209073
PMC: PMC2774875
OpenAlex: W2128057905
Cited by: 183
References: 65
Citations by year: 2026: 1 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 6 · 2020: 6 · 2019: 4 · 2018: 9 · 2017: 13 · 2016: 6 · 2015: 18 · 2014: 21 · 2013: 23 · 2012: 19
FWCI: 1.62
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: Journal of Leukocyte Biology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (AI048850)
Kentucky Lung Cancer Research Fund
The American Lung Association
Commonwealth of Kentucky Research Challenge Trust Fund
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Keywords: tumor-associated macrophages, macrophage reprogramming, macrophage polarization, IL-12, tumor growth, metastasis, immunosuppression, chronic inflammation, cancer immunotherapy
MeSH terms: Cell Differentiation, Humans, Immune System, Killer Cells, Natural, Macrophages, Monocytes, Neoplasms, Th1 Cells, Th2 Cells

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Functional plasticity of macrophages: in situ reprogramming of tumor-associated macrophages

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