Role of inflammation in cancer progression

Duke University, Durham NC

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): Recent advances have highlighted an important role for chronic inflammation in promoting tumor development. How chronic inflammation promotes tumor formation during the early stages of tumorigenesis remains unknown. In the preliminary studies, we investigated whether MyD88, a common adaptor for the innate immune signaling pathways, plays a role in the development of inflammation-induced, spontaneously developed hepatocellular carcinoma (HCC). We showed that hepatocyte-intrinsic MyD88 signaling is critical for the development of the precancerous dysplastic nodules and their progression to HCC. The objective of this application is to elucidate critical mechanisms governing the immune evasion by precancerous dysplastic lesions, leading to progression to HCC. Specifically, we hypothesize that precancerous dysplastic hepatocytes evade immune elimination by recruiting immunosuppressive inflammatory monocytes. We will test this hypothesis and pursue the critical tumor-derived factors involved in the recruitment of the immune suppressors. By providing how tumor-derived factors influence the anti-tumor immune response during the early time points of tumorigenesis, these studies will have profound implications in the development of new therapeutic targets for cancer prevention and therapy.