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Updated: Oct 6, 2025

A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
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A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells

Published on: May 6, 2018

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MerTK-mediated efferocytosis promotes immune tolerance and tumor progression in osteosarcoma through enhancing M2

Jinti Lin1,2, Ankai Xu1,2, Jiakang Jin1,2

  • 1Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, PR China.

Oncoimmunology
|January 17, 2022
PubMed

Insights

Efferocytosis, or the clearance of dead cells by macrophages, promotes osteosarcoma growth by enhancing immune suppression. Inhibiting MerTK blocks this process, reducing tumor growth and improving anti-tumor immunity.

Area of Science:

  • Immunology
  • Oncology
  • Cell Biology

Background:

  • Osteosarcoma immunotherapy has limited efficacy, necessitating understanding of immune tolerance mechanisms.
  • Efferocytosis (apoptotic cell clearance by phagocytes) suppresses immune responses and is prevalent in tumors.
  • Macrophages are abundant in osteosarcoma, suggesting efferocytosis as a potential therapeutic target.

Purpose of the Study:

  • To investigate the role of efferocytosis in osteosarcoma progression and immune evasion.
  • To identify the molecular pathways and receptors mediating efferocytosis in osteosarcoma.
  • To evaluate the therapeutic potential of inhibiting efferocytosis in osteosarcoma models.

Main Methods:

  • Verification of M2 macrophage polarization and PD-L1 expression post-efferocytosis.
  • Pharmacological inhibition and genetic knockdown of efferocytosis pathways.
  • Assessment of tumor progression and immune landscape in a murine osteosarcoma model.

Main Results:

  • Efferocytosis induced M2 polarization and PD-L1 expression in macrophages.
  • The MerTK receptor mediated efferocytosis, regulating macrophage phenotype via the p38/STAT3 pathway.
  • MerTK inhibition in vivo suppressed tumor growth, increased CD8+ T cell infiltration, and reduced T cell exhaustion.

Conclusions:

  • MerTK-mediated efferocytosis drives osteosarcoma progression through M2 macrophage polarization and PD-L1-induced immune tolerance.
  • Targeting MerTK represents a promising strategy to overcome immune evasion in osteosarcoma.
  • Understanding the p38/STAT3 pathway's role in efferocytosis offers further therapeutic avenues.
Keywords:
EfferocytosisM2 polarizationMerTKPD-L1immune toleranceosteosarcoma

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