The immune microenvironment in hepatocellular carcinoma: Identification of functional immune gene signatures associated with etiology or prognosis

B70 Although most tumors are immunogenic, the immune system is rarely able to block progression of established tumors. This is partly due to immunosuppressive mechanisms established within the tumor microenvironment. A better understanding of the composition, polarization, and function of the tumor immune microenvironment is important to design more effective treatments. The purpose of our studies is to describe the immune identity of human tumors, define how it may impact clinical end-points, and model how it is affected by treatment. Hepatocellular carcinoma is a highly aggressive cancer which is promoted by chronic liver inflammation, often caused by viral infections as Hepatitis B or C viruses (HBV or HCV). By transcriptome analysis and immunohistochemistry, we have analyzed the type and polarization of the immune cell infiltrate in the liver from patients with viral or non-viral-related tumors. Functional gene clusters associated with T cells, NK cells, inflammatory, myeloid or neutrophil signatures have been identified. Associations between chemokine/cytokine genes and markers of immune cell subsets suggest mechanisms responsible for recruitment and polarization of immune cells within the diseased liver. We found an important immune infiltration in non-malignant (but mostly cirrhotic or inflamed) liver tissues; the majority of the immune genes tested, and in particular the inflammation/myeloid signature, were on the other hand decreased in tumor samples. Among tumors with different etiology, the CD8/NK/NKT cell signature was significantly lower in tumors with non-viral etiology compared to those from HBV patients. HBV tumors are more heterogeneous with regard to their immune microenvironment; we are currently evaluating which factors are associated with these differences, including tumor stage, patient survival, and viral genotype.