The Origin of Tumor-Associated Macrophages and the Therapeutic Potential of Dual Targeting Ccr2 and Ccr5 as Therapy for Hepatocellular Carcinoma

Gut-Liver Immunopharmacology Unit

 

Project 3

The Origin of Tumor-Associated Macrophages and the Therapeutic Potential of Dual Targeting Ccr2 and Ccr5 as Therapy for Hepatocellular Carcinoma.
Project in collaboration with Prof. Dr. Hans Van Vlierberghe from the Hepatology Research Unit, dpt. Internal Medicine and Pediatrics.

Description

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide for which, in case of advanced disease, the current standard therapy has limited survival benefit. HCC is an inflammation-related cancer and the link between chronic inflammation and tumor development provides a promising target for the development of new HCC therapy. Macrophages are innate immune cells which dominate the tumor microenvironment and are defined as tumor associated macrophages (TAMs). TAMs represent a heterogeneous population with plastic functionality based on their origin and dynamic micro-environmental signals. However, how these cells originate and if their functions can be modified as therapeutic strategy for HCC has not been elucidated yet. Here, we will explore the contribution of distinct macrophage subsets to HCC development and to the population of TAMs in mouse and human HCC. As second objective, we will investigate the potential of targeting TAMs by dual blocking of CCR2 and CCR5 as treatment strategy for HCC. These chemokine receptors have an important role in the interaction between tumor, stromal and inflammatory cells during carcinogenesis. For the latter purpose, we will use well-selected mouse models and human explant tissue of HCC patients to approximate human disease as closely as possible. Our proposed set-up will lead to new fundamental scientific insights related to TAMs in HCC and how we can target those cells as therapeutic strategy.

Funding Ageny

 Stand up to Cancer, the Flemish cancer society

Contact

Lindsey Devisscher

Hans Van Vlierberghe, hans.vanvlierberghe@ugent.be