Cited by 101Phagocytosis and Immune RegulationCell death mechanisms and regulationAutophagy in Disease and Therapy

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Regulation of efferocytosis as a novel cancer therapy

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Zhou, Yunxiang, Yao, Yihan, Deng, Yongchuan, Shao, Anwen·2020·Cell Communication and Signaling

DOI 10.1186/s12964-020-00542-9PMC PMC7199874

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Abstract

Efferocytosis is a physiologic phagocytic clearance of apoptotic cells, which modulates inflammatory responses and the immune environment and subsequently facilitates immune escape of cancer cells, thus promoting tumor development and progression. Efferocytosis is an equilibrium formed by perfect coordination among “find-me”, “eat-me” and “don’t-eat-me” signals. These signaling pathways not only affect the proliferation, invasion, metastasis, and angiogenesis of tumor cells but also regulate adaptive responses and drug resistance to antitumor therapies. Therefore, efferocytosis-related molecules and pathways are potential targets for antitumor therapy. Besides, supplementing conventional chemotherapy, radiotherapy and other immunotherapies with efferocytosis-targeted therapy could enhance the therapeutic efficacy, reduce off-target toxicity, and promote patient outcome.

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Fig. 1 Schematic representation of signaling pathways in the efferocytosis-induced immune suppression for tumor progression. The engulfment of apoptotic cells by tumor-associated macrophages triggers a series of signaling pathways, subsequently induces M2 polarization of macrophages while inhibiting M1 polarization, increases Treg cells while decreasing CD8+ T cells, and thereby resulting in the inflammation resolution and immune suppression, which may provide an environment for cancer to escape from immunological surveillance and promote tumor progression. NFκB = factor-κ-gene binding; JAK/STAT1 = Janus kinase/signal transducers and activators of transcription 1; PI3K/Akt = phosphatidylinositol 3 kinase/protein-serine-threonine kinase; PD-1/PD-L1 = programmed death-ligand 1/programmed cell death protein 1; TLR = Toll-like receptor; IL = interleukin; TGFβ = transforming growth factor-beta; PGE2 = prostaglandin E2; PAF = platelet-activating factor; TNF-α = tumor necrosis factor-alpha; Treg cells = regulatory t cellCC BY · PubMed Central

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Additional file 7 of Inhibition of MER proto-oncogene tyrosine kinase by an antisense oligonucleotide enhances treatment efficacy of immunoradiotherapy
Hu, Y., Revenko, A. S., Barsoumian, H. B., Bertolet, G., Fowlkes, N. W., Maazi, H., Green, M. M., He, K., Sezen, D., Voss, T. A., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26689511
Additional file 6 of Inhibition of MER proto-oncogene tyrosine kinase by an antisense oligonucleotide enhances treatment efficacy of immunoradiotherapy
Hu, Y., Revenko, A. S., Barsoumian, H. B., Bertolet, G., Fowlkes, N. W., Maazi, H., Green, M. M., He, K., Sezen, D., Voss, T. A., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26689508
Additional file 1 of Extracellular vesicles containing MFGE8 from colorectal cancer facilitate macrophage efferocytosis
Ma, Z., Sun, Y., Yu, Y., Xiao, W., Xiao, Z., Zhong, T., Xiang, X., & Li, Z. (2024) · Figshare · doi:10.6084/m9.figshare.25909927
Additional file 5 of Inhibition of MER proto-oncogene tyrosine kinase by an antisense oligonucleotide enhances treatment efficacy of immunoradiotherapy
Hu, Y., Revenko, A. S., Barsoumian, H. B., Bertolet, G., Fowlkes, N. W., Maazi, H., Green, M. M., He, K., Sezen, D., Voss, T. A., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26689505
Additional file 4 of Extracellular vesicles containing MFGE8 from colorectal cancer facilitate macrophage efferocytosis
Ma, Z., Sun, Y., Yu, Y., Xiao, W., Xiao, Z., Zhong, T., Xiang, X., & Li, Z. (2024) · Figshare · doi:10.6084/m9.figshare.26726273
Additional file 8 of Inhibition of MER proto-oncogene tyrosine kinase by an antisense oligonucleotide enhances treatment efficacy of immunoradiotherapy
Hu, Y., Revenko, A. S., Barsoumian, H. B., Bertolet, G., Fowlkes, N. W., Maazi, H., Green, M. M., He, K., Sezen, D., Voss, T. A., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26689514
Additional file 3 of Extracellular vesicles containing MFGE8 from colorectal cancer facilitate macrophage efferocytosis
Ma, Z., Sun, Y., Yu, Y., Xiao, W., Xiao, Z., Zhong, T., Xiang, X., & Li, Z. (2024) · Figshare · doi:10.6084/m9.figshare.26726270
Additional file 1 of Inhibition of MER proto-oncogene tyrosine kinase by an antisense oligonucleotide enhances treatment efficacy of immunoradiotherapy
Hu, Y., Revenko, A. S., Barsoumian, H. B., Bertolet, G., Fowlkes, N. W., Maazi, H., Green, M. M., He, K., Sezen, D., Voss, T. A., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25347080
Additional file 2 of Inhibition of MER proto-oncogene tyrosine kinase by an antisense oligonucleotide enhances treatment efficacy of immunoradiotherapy
Hu, Y., Revenko, A. S., Barsoumian, H. B., Bertolet, G., Fowlkes, N. W., Maazi, H., Green, M. M., He, K., Sezen, D., Voss, T. A., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25347292
Additional file 4 of Inhibition of MER proto-oncogene tyrosine kinase by an antisense oligonucleotide enhances treatment efficacy of immunoradiotherapy
Hu, Y., Revenko, A. S., Barsoumian, H. B., Bertolet, G., Fowlkes, N. W., Maazi, H., Green, M. M., He, K., Sezen, D., Voss, T. A., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26689502
Additional file 1 of Interaction, immune infiltration characteristics and prognostic modeling of efferocytosis-related subtypes in glioblastoma
Zhao, S., Wang, Q., Liu, Y., Zhang, P., Ji, W., Xie, J., & Cheng, C. (2024) · Figshare · doi:10.6084/m9.figshare.26628304
Additional file 2 of Extracellular vesicles containing MFGE8 from colorectal cancer facilitate macrophage efferocytosis
Ma, Z., Sun, Y., Yu, Y., Xiao, W., Xiao, Z., Zhong, T., Xiang, X., & Li, Z. (2024) · Figshare · doi:10.6084/m9.figshare.25910168
Additional file 2 of Elucidation of the mechanisms underlying tumor aggravation by the activation of stress-related neurons in the paraventricular nucleus of the hypothalamus
Yoshida, S., Hamada, Y., Narita, M., Sato, D., Tanaka, K., Mori, T., Tezuka, H., Suda, Y., Tamura, H., Aoki, K., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22600334
Additional file 1 of Elucidation of the mechanisms underlying tumor aggravation by the activation of stress-related neurons in the paraventricular nucleus of the hypothalamus
Yoshida, S., Hamada, Y., Narita, M., Sato, D., Tanaka, K., Mori, T., Tezuka, H., Suda, Y., Tamura, H., Aoki, K., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22600331
Additional file 3 of Inhibition of MER proto-oncogene tyrosine kinase by an antisense oligonucleotide enhances treatment efficacy of immunoradiotherapy
Hu, Y., Revenko, A. S., Barsoumian, H. B., Bertolet, G., Fowlkes, N. W., Maazi, H., Green, M. M., He, K., Sezen, D., Voss, T. A., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26689499
Additional file 9 of Inhibition of MER proto-oncogene tyrosine kinase by an antisense oligonucleotide enhances treatment efficacy of immunoradiotherapy
Hu, Y., Revenko, A. S., Barsoumian, H. B., Bertolet, G., Fowlkes, N. W., Maazi, H., Green, M. M., He, K., Sezen, D., Voss, T. A., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26689517
YiQi-HuoXue prescription ameliorates LPS-induced sepsis-associated encephalopathy via VCAM-1–mediated microglial efferocytosis
Wang, Z., Song, E., Wang, Y., & Lu, Y. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1792688
Efferocytosis-related biomarkers and immune infiltration in pancreatic ductal adenocarcinoma based on single-cell sequencing and machine learning: a comprehensive bioinformatics analysis and experimental validation
Huang, S., Gu, D., & Xiong, W. (2026) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2026.153751
Microparticle uptake reduces efferocytic capacity of macrophages
Mishra, S., Aggarwal, B., Anant, P. S., Bajaj, A., & Jhunjhunwala, S. (2026) · Biomaterials Science · doi:10.1039/d5bm01447f
Construction of an efferocytosis related signature to predict the prognosis of pancreatic ductal adenocarcinoma
Li, J., Du, Z., Liu, X., Pan, T., Zheng, Y., & He, Y. (2026) · Discover Oncology · doi:10.1007/s12672-026-05088-9
Nanomedicine-enabled reprogramming of macrophage trained immunity to modulate cancer stem cells fate
Li, Y., Ge, Z., Sun, Y., Miao, L., Wang, P., Zhao, Y., Chai, S., Fan, B., Li, Y., Huang, W., et al. (2026) · Chinese Chemical Letters · doi:10.1016/j.cclet.2026.113105

Authors: Zhou, Y., Yao, Y., Deng, Y., & Shao, A.
Affiliations: Second Affiliated Hospital of Zhejiang University (CN)
Corresponding author: Deng, Yongchuan
Shao, Anwen
ORCID: Zhou, Yunxiang
Yao, Yihan
Deng, Yongchuan
Shao, Anwen
Venue: Cell Communication and Signaling
Publisher: Springer Science and Business Media LLC
Published: 2020-05-05
Volume: 18
Issue: 1
Pages: 71-71
ISSN: 1478-811X (ISSN-L)
DOI: 10.1186/s12964-020-00542-9
PMC: PMC7199874
OpenAlex: W3023079876
Cited by: 100
References: 146
Citations by year: 2026: 8 · 2025: 23 · 2024: 29 · 2023: 17 · 2022: 11 · 2021: 8 · 2020: 4
FWCI: 0.98
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Cell Communication and Signaling (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Postdoctoral Research Foundation of China (2017M612010)
National Natural Science Foundation of China (81701144)
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
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Keywords: efferocytosis, cancer immunotherapy, tumor immune evasion, find-me signals, eat-me signals, don't eat me signal, tumor microenvironment, drug resistance, combination therapy, cancer therapy targets
MeSH terms: Regulated Cell Death, Animals, Humans, Immunosuppression Therapy, Inflammation, Neoplasms, Phagocytosis, Apoptosis, Disease Progression, Tumor Escape

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