Abstract 4363: Tumor regulation of myeloid-derived suppressor cell proliferation, circulation and apoptosis.

Abstract

Abstract In response to stress, myeloid progenitor cells (MPCs) mobilize and establish sites of extramedullary hematopoiesis (EMH) within lymphoid and parenchymal organs. We report that the spleens of 4T1 mammary tumor-bearing (TB) mice are the primary site of MPC proliferation resulting in extensive EMH in association with decreased apoptosis, increased myeloid cell survival, and increased hematopoietic growth factor (GF) transcription by the tumor cells. MPC trafficking and survival differs between TB and naïve mice with leukocyte arrest in the lungs of naïve mice and accumulation in the splenic red pulp of TB mice with little marrow or tumor arrest or proliferation. Indeed, despite the high levels of GF transcription by tumor cells MDSC apoptosis in tumors is very high perhaps due to the high levels of NOS2 in the tumor microenvironment. Further myeloid proliferation directly correlates with the decrease in T-cell frequency, which is associated with extrathymic, but not thymic T-cell proliferation. In summary, tumor cytokines regulate a dynamic relationship between MPCs and T-cells regulating their proliferation, trafficking, accumulation, apoptosis, and survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4363. doi:1538-7445.AM2012-4363