Impact of the Innate Immune Checkpoint Inhibitor SIRPα-Fc on Immune Function

Signal regulatory protein α (SIRPα) is an inhibitory receptor expressed on myeloid cells that functions as a “healthy self-recognition” receptor by engagement with its ubiquitously expressed cell-surface ligand CD47. Disruption of the interaction between CD47 on primary human leukemia cells and SIRP on host macrophages with a decoy receptor SIRPα-Fc provokes robust leukemia cell phagocytosis and clearance. Because CD47 is widely expressed, we asked whether SIRPα-Fc administration may also impact the frequency and function of normal immune cells. To test this idea, NOD mice were treated with SIRPα-Fc and subjected to immunophenotypic, serum cytokine and complete blood cell count analyses. Modest alterations in dendritic cell (DC) populations and reduced levels of several inflammatory cytokines and platelets were observed in SIRPα-Fc compared to control Fc fusion protein-treated mice. SIRPα-Fc administration did not affect T cell activation or proliferation in a DC:T cell co-culture system suggesting safe use as an immunotherapy.M.Sc