A74 HELMINTH ANTIGENS OR REGULATORY MACROPHAGES REDUCE THE SEVERITY OF COLORECTAL CANCER

Abstract

Abstract Background Infection with helminth parasites is a potent stimulus of immunity, and murine model systems reveal that a bystander benefit of this response to helminths is suppression of colitis. Unraveling the mechanism of this inhibition of colitis, the regulatory macrophage has emerged as a cell of interest in ‘helminth therapy’. Given the relationship between inflammation and cancer – patients with inflammatory bowel disease (IBD) have a higher risk of colorectal cancer (CRC). Aims To test the hypothesis that intraperitoneal administration of excretory/secretory products from the tapeworm Taenia crassiceps (TcES) or IL-4-treated macrophages (M(IL-4)) (characteristic of the immune response to helminths) would affect the outcome of CRC. Methods CRC was induced in female BALB/c and male C57Bl/6 mice using azoxymethane (AOM) (10 mg, ip) and three cycles of Dextran sulfate sodium (DSS: 7 days, 1–2% wt./vol.) separated by 2 weeks of normal tap water. Following initiation of CRC, mice received TcES (200 μg, ip.) - or M(IL-4) (106, ip). On necropsy, CRC incidence, number, and size of the tumour were recorded and tumors assessed histologically. Results Mice receiving TcES or M(IL-4)s were substantially protected from AOM-DSS induced CRC, as shown by statistically significant reductions in tumor number and size, although the number of mice developing tumors was unchanged (n=4–8 mice). The suppression of CRC in TcES-treated mice correlated with reduced mobilization of STAT3 and NF-κB signaling cascades in the as determined by immunostaining and immunoblot of whole tissue extracts. Conclusions With the speculation that helminth-derived molecules or transfer of in vitro educated macrophages could be used to treat IBD comes the specter of the putative oncogenic effects of regulatory macrophages. Contrary to this, the data herein show that the TcES reduced CRC; and, that murine macrophages (M(IL4)) also actually limit the severity of inflammation-driven CRC by directly targeting the cancer cells or reducing the inflammatory stimulus. These findings add emphasis to the consideration of autologous regulatory macrophage transfer to treat IBD and CRC Funding Agencies CCCCONACYT (Mexico)