CD47 blockade synergizes with doxorubicin in enhancing macrophage phagocytosis of Ewing sarcoma cells and deceasing xenograft tumor growth and metastasis in an orthotopic model of Ewing sarcoma
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ABSTRACT: Macrophages are immune cells whose major functions include phagocytosing tumor cells. However, tumors escape macrophage phagocytosis through the expression of anti-phagocytic signals, most commonly CD47. Moreover, 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 utilize a CD47 blockade (magrolimab, MAG) to inhibit the anti-phagocytic signal and a chemotherapy regimen (doxorubicin, DOX) to enhance the pro-phagocytic signal and evaluated the effects of MAG or DOX alone and in combination on macrophage phagocytosis of ES cells in vitro and tumor formation and development in vivo. Furthermore, we performed RNA-Seq to identify potential mechanisms of resistance to the CD47 blockade combinatorial therapy.
ORGANISM(S): Homo sapiens/Mus musculus xenograft
PROVIDER: GSE244548 | GEO | 2024/06/19
REPOSITORIES: GEO
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