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Cited by 332Immune cells in cancerPhagocytosis and Immune RegulationCancer, Stress, Anesthesia, and Immune Response

The DOI matches its Crossref record; 188 of the 199 references it cites were found in a registry or an index.

The Role of Macrophages in Cancer Development and Therapy

Open access
Cendrowicz, Ewa, Sas, Zuzanna, Bremer, Edwin, Rygiel, Tomasz P.·2021·Cancers
DOI 10.3390/cancers13081946PMC PMC8073377
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Abstract

Macrophages are critical mediators of tissue homeostasis and influence various aspects of immunity. Tumor-associated macrophages are one of the main cellular components of the tumor microenvironment. Depending on their activation status, macrophages can exert a dual influence on tumorigenesis by either antagonizing the cytotoxic activity of immune cells or, less frequently, by enhancing antitumor responses. In most situations, TAMs suppress T cell recruitment and function or regulate other aspects of tumor immunity. The importance of TAMs targeting in cancer therapy is derived from the strong association between the high infiltration of TAMs in the tumor tissue with poor patient prognosis. Several macrophage-targeting approaches in anticancer therapy are developed, including TAM depletion, inhibition of new TAM differentiation, or re-education of TAM activation for cancer cell phagocytosis. In this review, we will describe the role of TAMs in tumor development, including such aspects as protumorigenic inflammation, immune suppression, neoangiogenesis, and enhancement of tissue invasion and distant metastasis. Furthermore, we will discuss therapeutic approaches that aim to deplete TAMs or, on the contrary, re-educate TAMs for cancer cell phagocytosis and antitumor immunity.

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Crossref · 10.3390/cancers13081946

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Figures

Figure 1 A spectrum of macrophage activation. The functional M1-M2 spectrum subdivisions of activated macrophages, derived from human monocytes or mouse bone marrow upon CSF-1 stimulation. Stimulation conditions are IL-4, immune complexes (Ic), IL-10, glucocorticoids (GC) with TGFβ, glucocorticoids alone, LPS, LPS and IFNγ, and IFNγ alone.
Figure 1 A spectrum of macrophage activation. The functional M1-M2 spectrum subdivisions of activated macrophages, derived from human monocytes or mouse bone marrow upon CSF-1 stimulation. Stimulation conditions are IL-4, immune complexes (Ic), IL-10, glucocorticoids (GC) with TGFβ, glucocorticoids alone, LPS, LPS and IFNγ, and IFNγ alone.CC BY · PubMed Central
Figure 2 Mechanisms of tumorigenesis stimulation by TAMs. TAMs play an important role in the process of tumorigenesis by induction of inflammation (top left loop), stimulation of neoangiogenesis (top right loop), immune suppression (bottom left loop), and induction of metastasis (bottom right loop). The figure was created with Biorender.com.
Figure 2 Mechanisms of tumorigenesis stimulation by TAMs. TAMs play an important role in the process of tumorigenesis by induction of inflammation (top left loop), stimulation of neoangiogenesis (top right loop), immune suppression (bottom left loop), and induction of metastasis (bottom right loop). The figure was created with Biorender.com.CC BY · PubMed Central
Figure 3 Strategies to target TAMs for anticancer therapy. Two main strategies are used to target TAMs in the TME, reduction of the number of macrophages in the tumor (top panel) or re-education of macrophages (bottom panel). Several molecular targets have been discovered to apply therapies targeting TAMs (mentioned in the figure), and various therapeutics have been developed that target these molecules, including small molecule inhibitors, monoclonal antibodies, soluble ligands, bispecific fusion proteins, and antibody fragments, and nanoparticles. The figure was created with Biorender.com.
Figure 3 Strategies to target TAMs for anticancer therapy. Two main strategies are used to target TAMs in the TME, reduction of the number of macrophages in the tumor (top panel) or re-education of macrophages (bottom panel). Several molecular targets have been discovered to apply therapies targeting TAMs (mentioned in the figure), and various therapeutics have been developed that target these molecules, including small molecule inhibitors, monoclonal antibodies, soluble ligands, bispecific fusion proteins, and antibody fragments, and nanoparticles. The figure was created with Biorender.com.CC BY · PubMed Central

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  1. Yue, 2010, NIH Public Access, Bone, 23, 1

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Metadata

Authors
Cendrowicz, E., Sas, Z., Bremer, E., & Rygiel, T. P.
Affiliations
  • University Medical Center Groningen (NL)
  • Medical University of Warsaw (PL)
Corresponding author
Rygiel, Tomasz P.
ORCID
Venue
Cancers
Publisher
MDPI AG
Published
2021-04-18
Volume
13
Issue
8
Pages
1946
ISSN
2072-6694 (ISSN-L)
DOI
10.3390/cancers13081946
PMC
PMC8073377
OpenAlex
W3156547118
Cited by
332
References
199
Citations by year
2026: 33 · 2025: 68 · 2024: 106 · 2023: 72 · 2022: 42 · 2021: 11
FWCI
5.91
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancers (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
Funders
Fundacja na rzecz Nauki Polskiej (TEAM TECH/2016-1/8)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Stress, Anesthesia, and Immune Response
Keywords
tumor-associated macrophages, tumor microenvironment, TAM depletion, TAM reprogramming, tumor immunosuppression, neoangiogenesis, metastasis, antitumor immunity, T cell recruitment

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