Exclusion of Notch from the contact site during efferocytosis restricts anticancer immunity - PubMed
3 hours ago
- #anticancer immunity
- #Notch signaling
- #efferocytosis
- Efferocytosis, the clearance of dying cells by phagocytes, is crucial for tissue homeostasis and suppressing inflammation but can create an immunosuppressive tumor microenvironment.
- Notch signaling is actively suppressed during efferocytosis; activating this pathway in myeloid cells enhances anticancer immunity in mice.
- Contact with dead cells or IgG-coated surfaces triggers an integrin barrier that excludes Notch from the contact site to prevent signaling.
- The integrin barrier formation requires the Rubicon-VPS34 complex, which recruits phospholipase D (PLD) to regulate integrin activation.
- Blocking Rubicon or inhibiting PLD increases Notch activation during efferocytosis, improving anticancer immunity in a Notch-dependent manner.
- This study reveals a regulatory mechanism that limits Notch signaling during efferocytosis, impacting anticancer immunity.