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Tumor-Associated Macrophages: From Mechanisms to Therapy
Open accessAbstract
The tumor microenvironment is a complex ecology of cells that evolves with and provides support to tumor cells during the transition to malignancy. Among the innate and adaptive immune cells recruited to the tumor site, macrophages are particularly abundant and are present at all stages of tumor progression. Clinical studies and experimental mouse models indicate that these macrophages generally play a protumoral role. In the primary tumor, macrophages can stimulate angiogenesis and enhance tumor cell invasion, motility, and intravasation. During monocytes and/or metastasis, macrophages prime the premetastatic site and promote tumor cell extravasation, survival, and persistent growth. Macrophages are also immunosuppressive, preventing tumor cell attack by natural killer and T cells during tumor progression and after recovery from chemo- or immunotherapy. Therapeutic success in targeting these protumoral roles in preclinical models and in early clinical trials suggests that macrophages are attractive targets as part of combination therapy in cancer treatment.
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“Accordingly, TAM-based therapeutic strategies are being developed that aim at TAM targeting, TAM re-education, and TAM depletion [88, 96, 101, 102].”
From Tumor microenvironment complexity and therapeutic implications at a glance (2020) · cites this paper as [88]
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“Many therapy strategies have attempted to alter the polarization of macrophages’ “re-programming” or prevent monocyte tumor infiltration (Noy and Pollard, 2014).”
From Sysrev: A FAIR Platform for Data Curation and Systematic Evidence Review (2021) · cites this paper as Noy and Pollard, 2014
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“In preclinical models, both of these innate immune cell types aid tumor growth and metastasis through their secretion of factors that suppress antitumor immune responses, especially those of CD8 + T cells and NK cells (166, 167).”
From Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance (2021) · cites this paper as [167]
In the citing paper
“The production of colony stimulating factor 1 (CSF-1; also known as macrophage colony stimulating factor) by BCCs, has been reported to stimulate the recruitment of macrophages to primary breast tumors, leading to the secretion by tumor-associated macrophages (TAMs) of epidermal growth factor, which binds to its cognate receptor on BCCs to stimulate invasion and metastasis [36–38].”
From The hypoxic tumor microenvironment: A driving force for breast cancer progression (2016) · cites this paper as [38]
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“Interestingly, CSF1 upregulates TIE2 on TAMs (Forget et al., 2014) indicating a link between CSF1, TIE2 macrophages, and the induction of the angiogenic switch.”
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Metadata
- Authors
- Noy, R., & Pollard, J. W.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Pollard, Jeffrey W.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 41
- Issue
- 1
- Pages
- 49-61
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC4137410
- OpenAlex
- W1971620413
- Cited by
- 4,089
- References
- 136
- Citations by year
- 2026: 258 · 2025: 326 · 2024: 359 · 2023: 393 · 2022: 485 · 2021: 479 · 2020: 424 · 2019: 379 · 2018: 297 · 2017: 285 · 2016: 215 · 2015: 157 · 2014: 27
- FWCI
- 22.25
- Type
- journal article
- Language
- en
- Update notices
- erratum (2014-11-20)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wellcome Trust (101067, 101067/Z/13/Z)
- National Institutes of Health (UL1TR001073)
- National Cancer Institute (P01CA100324, R01CA172451)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- tumor-associated macrophages, tumor microenvironment, tumor angiogenesis, tumor invasion, metastasis, pre-metastatic niche, immunosuppression, natural killer cells, T cells, macrophage-targeted therapy, combination cancer therapy
- MeSH terms
- Animals, Cell Movement, Cell Survival, Cell Transformation, Neoplastic, Humans, Immunosuppression Therapy, Macrophages, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms, Neovascularization, Pathologic, Cell Lineage, Cell Proliferation, Mice, Tumor Microenvironment
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