The DOI matches its Crossref record; 63 of the 65 references it cites were found in a registry or an index.
Functional plasticity of macrophages: in situ reprogramming of tumor-associated macrophages
Open accessAbstract
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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“It has been shown that unlike lymphocytes, where cellular phenotype is relatively fixed upon differentiation, macrophages have dynamic and plastic phenotypes that change with local microenvironmental signals [5,14–16].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [14]
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Metadata
- 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
- 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
- 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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