Abstract A80: Role of myeloid SOCS3 in prostate cancer progression.

Abstract

Abstract Suppressor Of Cytokine Signaling (SOCS) proteins, negative regulators of the JAK/STAT pathway, have been implicated in having a key protective role in tumor initiation and progression. However, the role of SOCS3 in regulating the differentiation and functions of myeloid-derived suppressor cells (MDSC) is poorly understood. Recent studies show the important role of MDSCs in promoting tumor progression as well as metastasis by regulating immune surveillance. To determine the role of myeloid SOCS3 in tumor progression, Conditional SOCS3 deletion in myeloid cells (LysMCre-SOCS3fl/fl) and SOCS3fl/fl C57BL/6 mice were used as recipients for subcutaneous transplantation of TRAMP-derived mouse prostate tumor cells. Our results indicate that tumor growth is significantly enhanced in myeloid-specific SOCS3-deficient mice, which correlates with elevated levels of Gr1+/CD11b+ cells in both spleen and tumor, and less CD8+ T-cell infiltration in tumors. Tumors from myeloid-specific SOCS3-deficient mice also express high levels of Arginase-1 and have elevated Akt signaling. In vitro, SOCS3-deficient bone-marrow-derived mononuclear cells (BDMC) exhibit heightened STAT3 activation and are subject to differentiation towards the MDSC phenotype. These findings suggest that myeloid cell SOCS3 provides protection from tumor progression by regulating MDSC differentiation. Citation Format: Hao Yu, Yudong Liu, Etty N. Benveniste, Hongwei Qin. Role of myeloid SOCS3 in prostate cancer progression. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A80.