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Figure 4. Targets to prioritize in combination with CD47 blockade. Targeting CD47 can alter immune effector response to the tumor microenvironment in a variety of ways. Where typically the interaction between SIRPα on the macrophage and CD47 on the tumor inhibits tumor cell phagocytosis by the macrophage (A), anti-CD47 antibodies can disrupt this interaction, permitting phagocytosis (B). This blockade of the CD47/SIRPα axis can be paired with other targeted antibody therapies, exemplified here with anti-GD2 antibody dinutuximab, to target tumor cells through the macrophage Fc receptor (C). T cells can be genetically engineered to express anti-CD47 CAR directly targeting CD47+ tumor cells for lysis (D). Similarly, natural killer cells can engage CD47+ tumor cells through antibody-dependent cellular cytotoxicity via anti-CD47 antibody interaction with the Fc receptor (E). CAR: chimeric antigen receptors; SIRPα: signal regulatory protein α