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.

Public Health Relevance

Chronic inflammation has been implicated in cancer progression. How the presence of chronic inflammation promotes cancer remains largely unknown. The proposed work will identify critical factors mediating the inflammation-associated cancer, and in turn will help us design more effective strategies for treating cancer as well as preventing relapses. Thus, it is highly cancer-relevant.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA186973-01
Application #
8750502
Study Section
Special Emphasis Panel (ZCA1-RTRB-Z (M2))
Program Officer
Howcroft, Thomas K
Project Start
2014-07-01
Project End
2016-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
$205,102
Indirect Cost
$74,602
Name
Duke University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705