Immunological characterization of oncogene-driven models of hepatocellular carcinoma. (100.19)

• Published in: The Journal of immunology (1950) 2010-04, Vol.184 (1_Supplement), p.100-100.19
• Main Authors: Scarzello, Anthony, Stauffer, Jim, Back, Tim, Subleski, Jeff, Weiss, Jonathan, Ortaldo, John, Wiltrout, Robert
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.184.Supp.100.19

Constitutively active AKT, MET, and beta-catenin (CAT) are initiating oncogenes that efficiently induce hepatic primary tumors when co-delivered; but not as single agents. Using a qPCR assay, we have begun to detail the early events of oncogene integration and to correlate the amount of integrated oncogene with developing tumor size. Furthermore, we found that the serum from mice injected with MET/CAT have elevated levels of alpha fetoprotein, a biomarker which has been similarly observed in advanced cases of HCC. Correlating the influx of infiltrating leukocytes and serum biomarker levels with the quantity of integrated oncogenes is critical to characterize their relative contributions to tumor progression. The profile of liver leukocytes in both MET/CAT and AKT/CAT murine models display phenotypes similar to those in HCC patients. By day 14, increased frequency and numbers of Tregs, MDSCs, as well as an up-regulation of PD-1 on CD4+ and CD8+ T cells was observed. The oncogene-driven tumor models described in this study exhibit many of the molecular and cellular events underlying HCC progression in humans. This molecularly defined approach to hepatocellular oncogenesis should enable us to characterize the contributions of inflammation in a primary tumor model with a defined oncogene signaling pathway.