Abstract 5030: Polarizing tumor associated macrophages (TAMs) towards an anti-tumor phenotype with a novel compound reveals a new subset of TAMs within breast tumors which facilitate tumor regression

Abstract

Abstract Manipulation of the innate immune system is a relatively understudied strategy for anti-cancer immunotherapy. The current focus on immunotherapy is centered on the adaptive immune system. However, there is growing evidence that manipulation of the innate immune system, including macrophages, is also a promising method to combat cancer. Tumor associated macrophages (TAMs) are one of the major infiltrating leukocyte populations associated with solid tumors. There are two major types of macrophages: classically activated macrophages, which can kill bacteria, pathogens, and similarly tumor cells; and alternatively activated macrophages which facilitate wound repair and are generally found in the tumor microenvironment. TAMs are generally alternatively activated cells with immunosuppressive properties that have been shown to enhance tumorogenesis by facilitating metastasis, angiogenesis, and inhibiting a protecting adaptive immune response. The presence of macrophages in the tumor microenvironment correlates with poor prognosis. Here we describe a novel, first in class compound that activates macrophages to an anti-tumor phenotype. While this compound has no direct cytotoxic activity, we show in the PyMT mouse model of breast cancer that breast tumors regress in response to therapy in a manner dependent on myeloid cells. Through the use of flow cytometry, we have been able to identify different subpopulations of TAMs using the markers CD45, MHCII, and CD11b. Correlating with tumor regression, we see an increase in PARP and cleaved caspase 3, indicating apoptotic cell death. Here we show that a novel compound effectively polarize macrophages to an anti-tumor phenotype to induce tumor regression. This strategy may have great therapeutic promise. Citation Format: Alaba O. Sotayo, Jennnifer L. Guerriero, Holly E. Ponichtera, Anthony G. Letai. Polarizing tumor associated macrophages (TAMs) towards an anti-tumor phenotype with a novel compound reveals a new subset of TAMs within breast tumors which facilitate tumor regression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5030. doi:10.1158/1538-7445.AM2015-5030