Disruption of CD47-SIRPα signaling restores inflammatory function in tumor-associated myeloid-derived suppressor cells
Carlo Zimarino, William E. Moody, Sarah E. Davidson, Hafsa Munir, Jacqueline D. Shields
Abstract
by exposing hematopoietic stem cells to tumor-derived factors. Engagement of CD47 with SIRPα on myeloid cells reduced their phagocytic capability, enhanced expression of immune checkpoints, increased reactive oxygen species production, and suppressed T cell proliferation. Perturbation of SIRPα signaling restored phagocytosis and antigen presentation by MDSCs, which was accompanied by renewed T cell activity and delayed tumor growth in multiple solid cancers. These data highlight that therapeutically targeting myeloid functions in combination with immune checkpoint inhibitors could enhance anti-tumor immunity.
Topics & Concepts
Myeloid-derived Suppressor CellCD47Function (biology)SuppressorMyeloid cellsCell biologyInflammationMyeloidCancer researchChemistryBiologyImmunologyCancerPhagocytosisGeneticsPhagocytosis and Immune RegulationImmune cells in cancerImmune Cell Function and Interaction