Related Experiment Video

Updated: Jun 2, 2026

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
08:01

Stimulation of Notch Signaling in Mouse Osteoclast Precursors

Published on: February 28, 2017

Exclusion of Notch from the contact site during efferocytosis restricts anticancer immunity

Zhenrui Li1, Beisi Xu2, Piyush Sharma3

  • 1Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA. Zhenrui.Li@stjude.org.

Nature Immunology
|March 3, 2026
PubMed

Insights

Phagocytes suppress Notch signaling during efferocytosis, a process crucial for tissue repair. Activating Notch signaling enhances anticancer immunity by overcoming this suppression.

Area of Science:

  • Immunology
  • Cell Biology
  • Cancer Research

Background:

  • Efferocytosis, the clearance of dying cells by phagocytes, maintains tissue homeostasis and suppresses inflammation.
  • However, efferocytosis can create an immunosuppressive tumor microenvironment, hindering anticancer immunity.

Purpose of the Study:

  • To investigate the regulation of Notch signaling during efferocytosis.
  • To explore the potential of modulating Notch signaling to enhance anticancer immunity.

Main Methods:

  • Studied Notch signaling dynamics during efferocytosis in myeloid cells.
  • Utilized ectopic expression of Notch intracellular domain and genetic ablation of Rubicon.
  • Investigated the role of the Rubicon-VPS34 complex and phospholipase D (PLD) in regulating integrin activation during efferocytosis.

Main Results:

  • Notch signaling is actively suppressed during efferocytosis via an integrin barrier.
  • This barrier formation requires the Rubicon-VPS34 complex and is regulated by PLD.
  • Enhancing Notch signaling by inhibiting this barrier improves anticancer immunity in mice.

Conclusions:

  • Identified a novel regulatory mechanism restricting Notch signaling during efferocytosis.
  • Demonstrated that modulating this mechanism can enhance anticancer immunity, offering potential therapeutic strategies.

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