Introduction: Type-I interferons (IFNs) have been used to treat several types of cancers including follicular lymphoma, hairy cell leukemia and chronic myeloid leukemia. Treatment with type-I IFNs is however associated with significant toxic side effects due to the ubiquitous expression of type-I IFN receptors. Type-III IFNs elicit similar cellular responses as type-I IFNs, but restricted expression of type-III receptors may limit potential side effects of treatment with type-III IFNs. A number of studies are now exploring the use of type-III IFNs, specifically IFN-k3, as anticancer agents. IFN-k4 is a newly discovered type-III IFN that is genetically regulated and produced in a subset of individuals. Previously, we showed that IFN-k4 inhibits proliferation in a hepatoma cell line, however its anticancer potential has not been explored in comparison to other type-III IFNs. Methods: We developed stable human hepatoma (HepG2) and B-cell lymphoma (Raji) cell lines, engineered to express either IFN-k4-GFP or IFN-k3-GFP upon induction by doxycycline. We compared antiproliferative activity of IFN-k3 and IFN-k4 by measuring BRDU incorporation before and after induction of IFN-k expression. We also compared cell viability, apoptosis, and changes in cell cycle between IFN-k3 and IFN-k4 expressing cell lines. RNAseq and pathway analysis were used to explore the antiproliferative effect induced by IFN-k4. We show that IFN-k4 has higher antiproliferative activity compared to IFN-k3 in Raji and HepG2 cell lines and this can be explained by inhibition of the cell cycle. IFN-k4 expressing cell lines showed increased apoptotic cell death compared to IFN-k3 expressing cell lines. We also show that antiproliferative activity of IFN-k4 may be a result of inhibition of the MAPK pathway. Conclusion: This study demonstrates that IFN-k4 has a more potent antiproliferative activity than IFN-k3 in hepatoma and B cell lymphoma cell lines and the anticancer potential of IFN-k4 should be further explored. Introduction: Interleukin-1b (IL-1b) is a potent proinflammatory cytokine that is implicated both in acute and chronic viral infection. Persistent hepatic inflammation is the hallmark of hepatitis C virus (HCV) infection wherein it serves as a platform for progressive liver injury and onset of liver cancer. We examined the role of IL-1b role in HCV-induced hepatic inflammation by first assessing the transcriptional profile of chronic HCV patient liver by next-gen sequencing (RNAseq) staged by inflammation and fibrosis score. (microenvironment) role of IRF5 in mammary tumor initiation and progression.
Output: P001 IFN-K4 HAS A POTENT ANTIPROLIFERATIVE ACTIVITY IN B-CELL LYMPHOMA AND HEPATOMA CELL LINES HCV CORE PROTEIN TRIGGERS IL-1B PRODUCTION VIA THE NLRP3 INFLAMMASOME P004 LOSS OF IRF5 INDUCES SPONTANEOUS MAMMARY TUMORIGEN- ESIS P005 PROTEOLYTIC ORIGIN OF THE SOLUBLE HUMAN IL-6R IN VIVO AND A DECISIVE ROLE OF N-GLYCOSYLATION DISTINCT ROLES FOR IRF5 IN MAMMARY EPITHELIAL CELLS AND HOST TUMOR IMMUNITY: LOSS OF IRF5 IN EITHER COMPART- MENT LEADS TO TUMORIGENESIS SEXUALLY DIMORPHIC ROLES OF STAT3 IN PEDIATRIC BRAIN CANCER P008 DISRUPTION OF PD-1/PD-L1 SIGNALING IN 2D VS. 3D COLORECTAL CANCER COCULTURE MODEL REVEALED BY RNAI HIGH THROUGH- PUT SCREEN