Hepatocellular carcinoma (HCC) is the paradigm of inflammation-associated cancer and the 4th cause of cancer death worldwide. It develops mainly on cirrhosis context and liver carcinogenesis is a multistep process with accumulation of genetic defects in hepatocytes leading to malignant transformation. Importantly, along these events, the immune microenvironment of the liver has been shown to be a critical element all along the process leading to liver tumorigenesis. In that context, we provided compelling evidence (in human and mouse models) that LECT2, a liver secreted factor, is a key player regulating HCC aggressiveness through the control of inflammatory monocytes infiltrating tumors. Our goal is to decipher the molecular and cellular functional cross-talk between preneoplasic and transformed hepatocytes with specific immune effectors under different contexts. We are particularly interested in understanding the functional role of factors able to corrupt immune response and specifically immunosurveillance mechanisms. Our work in both humans (cohort of patients) and mice (genetically engineered/diet-induced mouse models) aims at developing new innovative immunotherapeutic strategies for liver cancer and other liver diseases by targeting key control points of the immune system.
