Chronic Inflammation and Carcinogenesis

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

We have two projects in colon cancer that emerged from our previous focus on IL-7. One project involves IL-17A, IL-17 F and IL-22. These are cytokines that are produced by cells that strongly promote the intestinal inflammation that leads to colon cancer. It had not been determined where IL-17 or IL-22 is produced during this inflammatory response. We developed knockin reporter mice for the two IL-17 genes using two colors and for IL-22. This enabled us to visualize T cells and innate lymphocytes producing these critical inflammatory cytokines during bowel inflammation leading to colon cancer. These reporter mice have been sent to numerous labs around the world and are in use for investigating many immunological processes. A second project aims to inhibit the bowel inflammation leading to colon cancer. IL-27 is a suppressive cytokines that we have cloned into the food bacterium, Lactococcus lactis. These engineered bacteria were given orally to mice with three different models of experimentally-induced inflammatory bowel disease. IL-27 rescued all mice from disease and death and therefore is an extremely promising therapeutic. To investigate the mechanism of IL-27 therapy, we have also developed murine organoids derived from colon. Using cultures of organoids and inflammatory cells, we find that IL-27 acts on inflammatory macrophages, suppressing their ability to damage colon tissues. Currently we are characterizing a new L.lactis-IL-27 construct that is designed for human therapy.