Ovarian cancer modulates the immunosuppressive function of CD11b+Gr1+ myeloid cells via glutamine metabolism
Immature CD11b All studies were performed using the intraperitoneal ID8 syngeneic epithelial ovarian cancer mouse model. Myeloid cell depletion and immunotherapy were carried out using anti-Gr1 mAb, gemcitabine treatments, and/or anti-PD1 mAb. The treatment effect was assessed by a survival curve, in situ luciferase-guided imaging, and histopathologic evaluation. Adoptive transfer assays were carried out between congenic CD45.2 and CD45.1 mice. Immune surface and intracellular markers were assessed by flow cytometry. ELISA, western blot, and RT-PCR techniques were employed to assess the protein and RNA expression of various markers. Bone marrow-derived myeloid cells were used for ex-vivo studies. The depletion of Gr1 Our study shows that the ovarian cancer microenvironment can regulate the metabolism and function of immunosuppressive CD11b
Journal
Molecular MetabolismAuthors
Funding
Determining the mechanisms by which calorie restriction alters macrophage polarization to promote an anti-tumor environment in epithelial ovarian cancerNovel Regulation and Targeting of Macrophages Metabolism in Neuroinflammatory DisordersEndogenous metabolite restricts GM-CSF signaling pathway in pathogenic macrophages to ameliorate CNS AutoimmunityDetermining the mechanisms by which calorie restriction alters macrophage polarization to promote an anti-tumor environment in epithelial ovarian cancerU.S. Department of Defense Grant W81XWH-16-OCRP