Loss of SOCS3 in myeloid cells prolongs survival in a syngeneic model of glioma

摘要: In glioma, microglia and macrophages are the largest population of tumor-infiltrating cells, referred to as glioma associated (GAMs). Herein, we sought determine role Suppressor Cytokine Signaling 3 (SOCS3), a negative regulator Signal Transducer Activator Transcription (STAT3), in GAM functionality glioma. We utilized conditional model which SOCS3 deletion is restricted myeloid cell population. found that SOCS3-deficient bone marrow-derived display enhanced prolonged expression pro-inflammatory M1 cytokines when exposed tumor conditioned medium vitro. Moreover, delays intracranial growth increases survival mice bearing orthotopic tumors vivo. Although from with cells appear histologically similar control mice, observed loss results decreased M2 polarized macrophage infiltration tumors. Furthermore, increased CD8+ T-cell regulatory These findings demonstrate beneficial effect on suppressing growth, highlight importance immune microenvironment.