Chronic Inflammation and Carcinogenesis

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

The new Cancer Inflammation Program has inspired two new projects in colon cancer that diverge from our previous focus on IL-7. One project involves IL-17A , IL-17 F and IL-25. These are T cell cytokines that are produced by cells that strongly promote the intestinal inflammation that leads to colon cancer. It has not been determined where IL-17 and 25 are produced during this inflammatory response. We have developed knockin reporter mice for the two IL-17 genes using two colors and for IL-25. This will enable us to visualize cells producing these critical inflammatory cytokines during bowel inflammation leading to colon cancer. A second project aims to inhibit the bowel inflammation leading to colon cancer. IL-27 and IL-35 are suppressive cytokines that we have cloned into the food bacterium, Lactococcus lactis. These engineered bacteria were given orally to mice with experimentally-induced fatal IBD. IL-27 rescued all mice from IBD and death and therefore is an extremely promising therapeutic. The mechanism appears to be through secondary induction of the suppressive cytokine IL-10, and subsequent inhibition of many inflammatory cytokines such as IL-23 and IL-6.