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Cited by 156Phagocytosis and Immune RegulationCell death mechanisms and regulationAutophagy in Disease and Therapy

Efferocytosis in the tumor microenvironment

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Werfel, Thomas A., Cook, Rebecca S.·2018·Seminars in Immunopathology
DOI 10.1007/s00281-018-0698-5PMC PMC6223858
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Abstract

Within the course of a single minute, millions of cells in the human body will undergo programmed cell death in response to physiological or pathological cues. The diminished energetic capacity of an apoptotic cell renders the cell incapable of sustaining plasma membrane integrity. Under these circumstances, intracellular contents that might leak into the surrounding tissue microenvironment, a process referred to as secondary necrosis, could induce inflammation and tissue damage. Remarkably, in most cases of physiologically rendered apoptotic cell death, inflammation is avoided because a mechanism to swiftly remove apoptotic cells from the tissue prior to their secondary necrosis becomes activated. This mechanism, referred to as efferocytosis, uses phagocytes to precisely identify and engulf neighboring apoptotic cells. In doing so, efferocytosis mantains tissue homeostasis that would otherwise be disrupted by normal cellular turnover and exacerbated further when the burden of apoptotic cells becomes elevated due to disease or insult. Efferocytosis also supports the resolution of inflammation, restoring tissue homesostasis. The importance of efferocytosis in health and disease underlies the increasing research efforts to understand the mechanisms by which efferocytosis occurs, and how a failure in the efferocytic machinery contributes to diseases, or conversely, how cancers effectively use the existing efferocytic machinery to generate a tumor-tolerant, immunosuppressive tumor microenvironment. We discuss herein the molecular mechanisms of efferocytosis, how the process of efferocytosis might support a tumor 'wound healing' phenotype, and efforts to target efferocytosis as an adjunct to existing tumor treatments.

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  • Macrophages preferentially efferocytose cancer cells, and significant efforts are being made to inhibit efferocytosis therapeutically.

    “Indeed, macrophage cell therapy has faced a significant hurdle in that macrophages preferentially efferocytose cancer cells, and significant efforts are being made to inhibit efferocytosis therapeutically (37, 38).”

    From Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells (2026) · cites this paper as [37]

    The “Therapeutic targeting of efferocytosis in the setting of cancer” section describes inhibitors being developed to block efferocytosis, supporting the therapeutic-efforts claim. But the “Mechanisms of efferocytosis” section says phagocytes preferentially identify apoptotic cells rather than healthy cells; it does not say macrophages preferentially efferocytose cancer cells. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Werfel, T. A., & Cook, R. S.
Affiliations
Vanderbilt University (US)
Corresponding author
Cook, Rebecca S.
ORCID
Venue
Seminars in Immunopathology
Publisher
Springer Science and Business Media LLC
Published
2018-09-05
Volume
40
Issue
6
Pages
545-554
ISSN
  • 1863-2297 (ISSN-L)
  • 1863-2300
DOI
10.1007/s00281-018-0698-5
PMC
PMC6223858
OpenAlex
W2890156794
Cited by
156
References
19
Citations by year
2026: 21 · 2025: 22 · 2024: 22 · 2023: 27 · 2022: 17 · 2021: 24 · 2020: 16 · 2019: 6 · 2018: 1
FWCI
1.20
Type
journal article
Language
en
Open access
Licence
Locations
  • Seminars in Immunopathology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (P50 CA098131)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
efferocytosis, tumor microenvironment, secondary necrosis, phagocytes, inflammation resolution, immunosuppression, tissue homeostasis
MeSH terms
Animals, Humans, Macrophages, Neoplasms, Phagocytes, Phagocytosis, Biomarkers, Apoptosis, Tumor Microenvironment

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