Figure 2.

Proposed Mechanisms of Targeting CD47. CD47 blockade decreases the anti-phagocytic “don’t-eat-me” signal on leukemia cells. Azacitidine may upregulate pro-phagocytic signals, such as calreticulin, increasing the likelihood of phagocytosis of leukemia cells. This may be further increased if CD47 binding to SIRPα is blocked or an antibody targeting a leukemic antigen (e.g., CD33) is present to bind a macrophage Fcγ receptor. Phagocytosis may lead to tumor peptide presentation to the adoptive immune system, multiple targets exist to increase T-cell activation such as antibodies to PD-L1 or to PD-1.