Abstract 460: Novel compound elicits anti-tumor macrophages associated with tumor regression in breast cancer

Abstract

Abstract Cancer immuno-therapies targeting components of the immune system have shown great promise for the treatment of various forms of cancer. Most of the immuno-therapies currently under trial intervene in adaptive immune cell pathways; however, the innate immune system has also recently been shown to play a potent immunomodulatory role in the tumor microenvironment. Tumor associated macrophages (TAMs) compose up to 50% of tumor volume. Presently, we demonstrate that administration of a novel compound stimulates rapid tumor regression that is associated with the infiltration of F4/80+ macrophages into tumors in the MMTV-PyMT murine model of breast cancer. A significant increase in tumor-infiltrating macrophages was visible by immunohistochemistry after five days of treatment and macrophages were necessary for tumor regression as demonstrated by cell depletion assays in vivo. Of note, macrophage infiltration correlated with an increase in tumor cell death as shown by elevated expression of the apoptotic protein cleaved-caspase-3 (CC3); conversely, cell proliferation factor Ki67 was decreased. Additionally, compound-treated animals exhibited striking changes in tumor vascularization, with a marked decrease in overall endothelial cell marker expression as displayed by immunohistochemistry. Taken together, these findings reveal a novel role for macrophages in breast tumor regression during treatment with a novel compound that alters the tumor microenvironment. Citation Format: Holly E. Ponichtera, Jennifer L. Guerriero, Alaba O. Sotayo, Anthony Letai. Novel compound elicits anti-tumor macrophages associated with tumor regression in breast cancer. [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 460. doi:10.1158/1538-7445.AM2015-460