Targeting CD47 enhanced the antitumor immunity of PD-L1 blockade in B-cell lymphoma.

Only a subset of B-cell lymphoma (BCL) patients can benefit from immune checkpoint inhibitors targeting PD-1/PD-L1. In the A20 model, SIRPα-Fc and anti-PD-L1 were employed to target CD47 and PD-L1 simultaneously. Flow cytometry, immunofluorescence and quantitative polymerase chain reaction were used to unravel the potential mechanisms. Simultaneously targeting CD47 and PD-L1 activated CD8 T cells with an increased release of effector molecules. Furthermore, infiltration of F4/80iNOS M1 macrophages was enhanced by the dual therapy. Anti-CD47 therapy could sensitize BCL tumors to anti-PD-L1 therapy in a CD8 T-cell- and M1-macrophage-dependent manner by promoting cytotoxic lymphocyte infiltration, which may provide a potential strategy for BCL treatment by simultaneously targeting CD47 and PD-L1.