Abstract 1511: Macrophage aggressiveness in the lung tumor microenvironment

Abstract

Abstract Macrophages are highly versatile phagocytes active in multiple roles in the immune system of vertebrates. However, within the tumor microenvironment, macrophages initiate and are exposed to a variety of cell signals. Some of these signals are involved in tumor growth, angiogenesis, and metastasis, and have been shown to alter macrophage function. These tumor associated macrophages display characteristics that indicate polarization from M1 to M2 phenotypes, and have been shown to promote angiogenesis and metastasis in cancer patients. In addition, clinical trials have shown that a high macrophage count in breast cancer patients is associated with a poor prognosis. We hypothesize that the engulfment ability and aggressiveness of macrophages incubated with lung cancer cells will be down regulated. Human mononuclear phagocytotic U937 cells were differentiated to macrophages by exposure to phorbol-12-myristate-13-acetate (PMA). These cells were then marked with APC fluorochrome dye for identification, and phagocytic activity was measured using PE conjugated fluorescent beads. Macrophages were incubated with two lung cancer cell lines (A549, H460) for various times and phagocytic indices were quantified using flow cytometry. Preliminary results indicated no change in phagocytic activity after 1 hour of exposure, and a 15% down regulation of overall engulfment after 24 hours of contact. These results were compared to cells incubated with non-cancerous lymphocytes, where there was no change in overall phagocytic activity. These data also indicated that the majority of normal macrophages were highly aggressive (engulfing 3 or more beads when analyzed by flow cytometry), but macrophages that were incubated with cancer cell lines experienced a statistically significant down regulation in aggressiveness, where the number of macrophages which engulfed 3 or more beads was reduced by 30% (p = 0.044). These findings indicate that exposure of U937-derived macrophages to lung cancer cell lines resulted in a possible shift towards the M2 phenotype. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1511. doi:10.1158/1538-7445.AM2011-1511