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Targeting phagocytosis checkpoints for cancer immunotherapy
André Veillette1,2,3, Jiaxin Li4,5, Cristian Camilo Galindo4,5
1Laboratory of Molecular Oncology, Institut de recherches cliniques de Montréal (IRCM), Montreal, Quebec, Canada. andre.veillette@ircm.qc.ca.
Nature Reviews. Cancer
|December 8, 2025
Summary
Macrophages use phagocytic checkpoints to eliminate cancer cells. Blocking inhibitory checkpoints like SIRPα/CD47 shows promise but faces challenges in efficacy and safety for cancer therapy.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Macrophages play a crucial role in cancer cell elimination via phagocytosis.
- Phagocytosis is regulated by pro-phagocytic and inhibitory receptors on macrophages.
- Targeting inhibitory phagocytic checkpoints, such as SIRPα/CD47, is a potential cancer therapeutic strategy.
Purpose of the Study:
- To review the evidence supporting phagocytic checkpoints as cancer therapy targets.
- To highlight current challenges and limitations in this therapeutic approach.
- To provide recommendations for improving efficacy and safety.
Main Methods:
- Review of pre-clinical and clinical studies on phagocytic checkpoints in cancer.
- Analysis of data on pro-phagocytic and inhibitory receptor functions.
- Examination of therapeutic strategies involving checkpoint blockade.
Main Results:
- Pro-phagocytic receptors (Fc receptors, MAC-1, SLAMF7) aid tumor cell elimination.
- Fc receptors are critical for monoclonal antibody anti-tumor efficacy.
- Blocking SIRPα/CD47 is a promising, yet challenged, therapeutic avenue due to efficacy and toxicity concerns.
Conclusions:
- Phagocytic checkpoints represent a viable target for cancer immunotherapy.
- Overcoming current challenges in efficacy and toxicity is essential for clinical success.
- Future research should focus on optimizing strategies for enhancing safety and effectiveness.
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