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Peer-reviewedCC BYMedComm

The Efferocytosis-Driven Macrophage Polarization: A Concerto in the Tumor Immunosuppressive Microenvironment.

  • Qiuping Chen1,2
  • Chunzhi Wu3
  • Changquan Huang4
  • Hang Zhou1
4 affiliations
  1. 1School of Basic Medical Sciences Chengdu University of Traditional Chinese Medicine Chengdu China.
  2. 2Department of Gastroenterology The First Medical Center Chinese PLA General Hospital Beijing China.
  3. 3Department of Oncology Chengdu Sixth People's Hospital Chengdu China.
  4. 4West China School of Medicine Sichuan University Affiliated Chengdu Second People's Hospital Chengdu China.
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Abstract

Efferocytosis plays a critical role in maintaining tissue homeostasis and controlling inflammation. However, in the tumor microenvironment, this process is hijacked to promote immune suppression. Treatments like radiotherapy and chemotherapy lead to widespread tumor cell death, which triggers efferocytosis and drives macrophages into an immunosuppressive state, allowing the tumor to evade the immune system and resist treatment. Nonetheless, the way efferocytic signals alter macrophage function and promote protumor effects during the recognition, engulfment, and digestion of apoptotic cells remains largely unclear. Therefore, this review thoroughly examines the influence of signaling molecules during the three stages of efferocytosis on macrophage phenotype and function. Subsequently, we explore the impact of polarized M2-type macrophages on shaping the immunosuppressive tumor microenvironment and regulating the development of drug resistance. Additionally, we critically evaluate the current status of clinical translation of efferocytosis receptor-related drugs and analyze the potential reasons for their synergistic or antagonistic interactions with chemotherapy and immunotherapy. This study provides a comprehensive understanding of the regulatory mechanisms of efferocytosis in macrophage polarization, enhancing knowledge of the fundamental mechanisms underlying tumor immune evasion and offering important guidance for the development of anticancer therapies targeting the efferocytosis process.

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Cite

BibTeXRIS
BibTeX
@article{chen2026efferocytosisdriven,
  title = {{The Efferocytosis-Driven Macrophage Polarization: A Concerto in the Tumor Immunosuppressive Microenvironment.}},
  author = {Qiuping Chen and Chunzhi Wu and Changquan Huang and Hang Zhou},
  journal = {MedComm},
  year = {2026},
  month = oct,
  doi = {10.1002/mco2.71038},
  url = {https://europepmc.org/article/MED/42899246},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - The Efferocytosis-Driven Macrophage Polarization: A Concerto in the Tumor Immunosuppressive Microenvironment.
AU  - Qiuping Chen
AU  - Chunzhi Wu
AU  - Changquan Huang
AU  - Hang Zhou
PY  - 2026
DA  - 2026/10/19
JO  - MedComm
DO  - 10.1002/mco2.71038
UR  - https://europepmc.org/article/MED/42899246
AB  - Efferocytosis plays a critical role in maintaining tissue homeostasis and controlling inflammation. However, in the tumor microenvironment, this process is hijacked to promote immune suppression. Treatments like radiotherapy and chemotherapy lead to widespread tumor cell death, which triggers efferocytosis and drives macrophages into an immunosuppressive state, allowing the tumor to evade the immune system and resist treatment. Nonetheless, the way efferocytic signals alter macrophage function and promote protumor effects during the recognition, engulfment, and digestion of apoptotic cells remains largely unclear. Therefore, this review thoroughly examines the influence of signaling molecules during the three stages of efferocytosis on macrophage phenotype and function. Subsequently, we explore the impact of polarized M2-type macrophages on shaping the immunosuppressive tumor microenvironment and regulating the development of drug resistance. Additionally, we critically evaluate the current status of clinical translation of efferocytosis receptor-related drugs and analyze the potential reasons for their synergistic or antagonistic interactions with chemotherapy and immunotherapy. This study provides a comprehensive understanding of the regulatory mechanisms of efferocytosis in macrophage polarization, enhancing knowledge of the fundamental mechanisms underlying tumor immune evasion and offering important guidance for the development of anticancer therapies targeting the efferocytosis process.
SN  - 2688-2663
ER  -