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