Abstract 1657: How does the tumor microenvironment affect macrophage aggressiveness
Authors: Weagel Evita G. , Liu Ping Guo , Meng Wei , Smith Curren D. , Robison Richard A. , O'Neill Kim L. 
Published: May 2015

The immune system plays an important role in the development and progression of cancer. In fact, immune cell infiltration can affect malignancy progression and metastasis. Infiltration of macrophages to the tumor site has been shown to account for more than 50% of the tumor mass in some breast cancers suggesting macrophages have a significant role in tumor progression. Macrophages are cells derived from the myeloid lineage and belong to the innate immune system. They differentiate from blood monocytes in tissue and one of their main functions is to phagocytose microbes and clear cellular debris. Macrophages also play an important role in inflammation and the resolution of inflammation. They exhibit a variety of responses depending on the type of stimuli they receive, varying from pro-inflammatory to anti-inflammatory. Two major macrophage phenotypes have been proposed: M1 and M2. M1 macrophages, or classically activated macrophages, show a pro-inflammatory profile that is characterized by aggressive phagocytosis and anti-microbial properties. M2 macrophages, also known as alternatively activated macrophages, exhibit immunomodulatory, repair, and angiogenic properties.

This project explored macrophage function by studying the aggressiveness of macrophages exposed to different cancer cell lines (Raji, H460, MCF7, MDA-MB-231, HT-29, SW620, and PC3) and their spent media. We used PMA-stimulated U937 cells and monocyte-derived macrophages from human blood as phagocytes. Macrophage aggressiveness was measured through flow cytometry by quantification of macrophage engulfment rates of fluorescent spherical beads. We found that cancer cell lines with higher aggressiveness had a more radical suppression of macrophage engulfment (81% engulfment reduction compared to control) than less aggressive cell lines (1% engulfment reduction compared to control). We also found that spent media had a lower effect on macrophage engulfment overall, indicating cell to cell contact is important to suppress macrophage engulfment. Spent media from aggressive cell lines had a similar effect to the cells themselves, suggesting cytokine and vesicle communication. We also studied how these cell lines affected macrophage polarization by qPCR, finding that lower engulfment rates correlate with an M2 cytokine profile (high IL-10, low IL-12) and higher engulfment rates correlate with an M1 cytokine profile (low IL-10, high IL-12). Further studies will help us understand more of the signals that cancer cells give to their environment to prevent macrophage engulfment and to help maintain an M2 phenotype.

Citation Format: Evita G. Weagel, Ping Guo Liu, Wei Meng, Curren D. Smith, Richard A. Robison, Kim L. O'Neill. How does the tumor microenvironment affect macrophage aggressiveness. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1657. doi:10.1158/1538-7445.AM2014-1657