The signal-regulatory protein CD47 mediates a “don't eat me” signal when it binds its receptor SIRPa, and this is thought to contribute to the resistance of tumors to phagocyte-dependent clearance. In Nature Medicine, Xu and colleagues show that therapeutic blockade of CD47 also leads to the activation of potent anti-tumor cytotoxic T lymphocyte (CTL) responses. Using syngeneic mouse tumor models, the authors find that blocking CD47 allows the sensing of tumor DNA and then triggers type I interferons. Acting on tumor-infiltrating dendritic cells, the type I interferons then drive the cross-presentation of tumor antigens to CTLs. These CTLs are essential for the anti-tumor effects of CD47 blockade. Therefore, in addition to simply preventing the phagocytosis of tumor cells, the CD47-SIRPa axis also protects tumors from destructive CTL responses. These findings reveal a new perspective on the underlying mechanism of therapeutic CD47 blockade.
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Fehervari, Z. Don't eat me, activate me. Nat Immunol 16, 1113 (2015). https://doi.org/10.1038/ni.3303