Alpha-Fetoprotein- and CD40Ligand-Expressing Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma.

Dendritic cells (DC) as professional antigen presenting cells are able to prime T-cells against the tumor-associated antigen α-fetoprotein (AFP) for immunotherapy of hepatocellular carcinoma (HCC). However, a strong immunosuppressive tumor environment limits their efficacy in patients. The co-stimulation with CD40Ligand (CD40L) is critical in the maturation of DC and T-cell priming.

Long term intravital multiphoton microscopy imaging of immune cells in healthy and diseased liver using CXCR6.Gfp reporter mice.

Liver inflammation as a response to injury is a highly dynamic process involving the infiltration of distinct subtypes of leukocytes including monocytes, neutrophils, T cell subsets, B cells, natural killer (NK) and NKT cells. Intravital microscopy of the liver for monitoring immune cell migration is particularly challenging due to the high requirements regarding sample preparation and fixation, optical resolution and long-term animal survival. Yet, the dynamics of inflammatory processes as well as cellular interaction studies could provide critical information to better understand the initiation, progression and regression of inflammatory liver disease.

Distinct anti-tumoral functions of adaptive immune cells in liver cancer.

Hepatocellular carcinoma (HCC) commonly arises in chronically inflamed livers, but may also provoke (anti-tumoral) immune responses. Using non-inflammatory diethylnitrosamine (DEN)-induced liver cancer in mice, we demonstrate that distinct axes of the adaptive immune system, which are also prognostic in human HCC, actively suppress hepatocarcinogenesis by controlling tumor formation and progression.

Serum NT-proCNP concentrations are elevated in patients with chronic liver diseases and associated with complications and unfavorable prognosis of cirrhosis.

Objectives: C-type natriuretic peptide (CNP) might be an important regulator of vasodilatation, fluid and sodium balance in liver cirrhosis. We aimed at assessing its regulation and prognostic relevance in liver disease patients.

Design And Methods: We analyzed NT-proCNP serum levels in 193 patients with chronic liver diseases and 43 healthy controls.

Adaptive immunity suppresses formation and progression of diethylnitrosamine-induced liver cancer.

Background: Hepatocellular carcinoma (HCC) is a typical inflammation-associated cancer, but may also provoke antitumour immune responses whose significance and underlying mechanisms are incompletely understood.

Objective: To characterise immune responses in the diethylnitrosamine (DEN)-liver cancer mouse model.

Design: Tumour development and immune cell functions upon DEN treatment were compared between C57BL/6 wild-type (WT), chemokine scavenging receptor D6-deficient, B cell- (Igh6), CD4 T cell- (MHC-II) and T-/B cell-deficient (Rag1) mice.

Inhibition of hepatitis C virus gene expression by adenoviral vectors encoding antisense RNA in vitro and in vivo.

Background & Aims: In this study, adenoviral vectors encoding an antisense RNA complementary to the 5' non-coding region (5'NCR) of the HCV-genome were generated to inhibit HCV-RNA gene expression in cell culture and in vivo.

Methods: First and second-generation (with E4-deletion) adenoviruses encoding the HCV5'NCR in antisense direction (Ad-NCRas and Ad-E4del-NCRas) were generated. Inhibition of HCV gene expression was analyzed in hepatoma cells stably transfected with the HCV5'NCR cDNA fused to the firefly luciferase gene (NCRluc), as well as in the HCV subgenomic replicon (genotypes 1b and 2a) and the fully infectious HCV JFH-1 cell culture systems.

Patient-derived dendritic cells transduced with an a-fetoprotein-encoding adenovirus and co-cultured with autologous cytokine-induced lymphocytes induce a specific and strong immune response against hepatocellular carcinoma cells.

Background/aims: Breaking immunologic tolerance towards the hepatocellular carcinoma (HCC)-associated alpha-fetoprotein (AFP) antigen is possible. The use of this potential for the treatment of immunocompromised HCC patients is limited. In this study, we analyzed whether dendritic cells (DCs) from HCC patients transduced with a human AFP (hAFP)-expressing adenovirus and co-cultured with cytokine-induced killer (CIK) cells can induce a strong specific immune response against HCC-cells.