Abstract B32: Myeloid-derived suppressor cell depletion augments antitumor activity in ovarian cancer

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are increased in tumors and create an immunosuppressive environment by inhibiting the T-cell function. In addition, MDSCs promote angiogenesis, tumor invasion, and metastasis. Increased MDSC accumulation in epithelial ovarian cancer (EOC) has been associated with poor prognosis. Our study investigated whether depletion of MDSCs will influence EOC progression and enhance the therapeutic response of programmed death-1 (PD1) immunotherapy. The intraperitoneal ID8 syngeneic mouse epithelial ovarian cancer cell model in B6 mice was used for the study. The ID8 tumor-bearing mice were treated once a week with either the anti-Gr1 specific monoclonal antibody (Ly6G/Ly6C mAb) that targets and depletes MDSCs, or its isotype IgG2b mAb as control (100µg/dose/mouse). Mice were sacrificed at day 60 for tumor burden evaluation. Quantification of various immune cells and their effector cytokines in blood, spleen, bone marrow, ascites, and tumor were performed by fluorescence-activated cell sorter (FACS) using specific cell surface and intracellular markers, ELISA, and by immunohistochemistry (IHC). The preclinical trial of anti-GR1 and anti-PD1 Ab combination was also carried out. ID8-bearing mice exhibited significantly higher levels of MDSCs (CD11bGr1+) (p Citation Format: Sharif Sakr, Sajad Dar, Shailendra Giri, Adnan Munkarah, Ramandeep Rattan. Myeloid-derived suppressor cell depletion augments antitumor activity in ovarian cancer. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr B32.