Abstract 1300: Breast cancer-associated macrophages undergo proliferation at different rates across ethnicities: results of a pilot study

Abstract

Abstract The tumor microenvironment is a complex biosystem composed of diverse cells, including tumor, immune and non-immune stromal cells. It has become increasingly clear that stromal cells have critical roles in tumor progression. Among the immune stromal cells, tumor-associated macrophages (TAM) are found in abundance, playing critical roles in tumor progression and are signs of poor prognosis. Whereas in chronic inflammation of a tissue M1 pro-inflammatory macrophages may play a role in tumor initiation, in advanced tumors, TAMs promote anti-inflammatory functions including suppression of immunity, tumor invasion, angiogenesis, metastasis, and resemble the behavior of M2 anti-inflammatory macrophages. CD163 is considered a human pan macrophage marker and has been extensively used in TAMs recognition in human tumors. Until recently, macrophages were considered end-differentiated cells without mitotic activity. However, more recently proliferative activity of macrophages has been identified in several settings, but not in tumors. In a recent study, we demonstrated that breast cancers from different ethnicities exhibit diverse degree of TAMs colonization. African American (AA) and Latina (LA) patients present with more aggressive tumors and lower survival rates than Caucasian (CA) women. We recently demonstrated that AA breast cancer patients exhibit tumors with very high numbers of macrophages, followed by LA, with CA showing the lowest numbers of TAMs. Consequently, in the present study we sought to examine whether the high numbers of TAMs detected in these cancer health disparity groups were associated with macrophage capacity to proliferate. To assess TAM mitotic potential, the Ki-67 nuclear marker was used. To examine this question, we carried out a pilot study with a small number of cases where the co-expression levels of Ki-67 and CD163 were determined by immunofluorescence (IF) in sections of human breast cancers from a retrospective breast cancer tumor bank encompassing these three ethnicities. Our results reveal that tumors from AA patients contain the highest numbers of CD163+/Ki-67+ cells among the three ethnic groups, followed by LA, with CA exhibiting the lowest numbers, thus paralleling our results with TAM numbers in these same ethnicities. As far as we know, this is the first report of macrophage proliferation in a tumor microenvironment, and particularly in association with ethnicity cancer disparity groups. Citation Format: Lidia G. Sanchez, Jorge E. Torrez-Munoz, Ana M. Santander, Tan A. Ince, Marta Torroella-Kouri. Breast cancer-associated macrophages undergo proliferation at different rates across ethnicities: results of a pilot study. [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 1300. doi:10.1158/1538-7445.AM2015-1300