biostudies-literatureUnknown43(1)Luo W<h4>Background</h4>Macrophages play important roles in phagocytosing tumor cells. However, tumors escape macrophage phagocytosis in part through the expression of anti-phagocytic signals, most commonly CD47. In Ewing sarcoma (ES), we found that tumor cells utilize dual mechanisms to evade macrophage clearance by simultaneously over-expressing CD47 and down-regulating cell surface calreticulin (csCRT), the pro-phagocytic signal. Here, we investigate the combination of a CD47 blockade (magrolimab, MAG) to inhibit the anti-phagocytic signal and a chemotherapy regimen (doxorubicin, DOX) to enhance the pro-phagocytic signal to induce macrophage phagocytosis of ES cells in vitro and inhibit tumor growth and metastasis in vivo.<h4>Methods</h4>Macrophages were derived from human peripheral blood mJournal of experimental & clinical cancer research : CR193https://www.ebi.ac.uk/biostudies/studies/S-EPMC11238356biostudies-literatureCombinatorial macrophage induced innate immunotherapy against Ewing sarcoma: Turning "Two Keys" simultaneously.PMC11238356Liao YRosenblum JMCostello HWijeratne SCassady KAZhu HHoang HCairo MSAyello JMiller KEChemnitz WMardis ERGandhi RCripe TPLuo WXu SGardenswartz ALee DAMo XGarfinkle EARfalseCombinatorial macrophage induced innate immunotherapy against Ewing sarcoma: Turning "Two Keys" simultaneously.<h4>Background</h4>Macrophages play important roles in phagocytosing tumor cells. However, tumors escape macrophage phagocytosis in part through the expression of anti-phagocytic signals, most commonly CD47. In Ewing sarcoma (ES), we found that tumor cells utilize dual mechanisms to evade macrophage clearance by simultaneously over-expressing CD47 and down-regulating cell surface calreticulin (csCRT), the pro-phagocytic signal. Here, we investigate the combination of a CD47 blockade (magrolimab, MAG) to inhibit the anti-phagocytic signal and a chemotherapy regimen (doxorubicin, DOX) to enhance the pro-phagocytic signal to induce macrophage phagocytosis of ES cells in vitro and inhibit tumor growth and metastasis in vivo.<h4>Methods</h4>Macrophages were derived from human peripheral blood m2024-01-01T00:00:00Z2024 Jul2026-06-01T13:31:38.639Z2026-04-08T13:10:42.91ZS-EPMC112383563899265910.1186/s13046-024-03093-w