Type I IFN receptor type 2 (IFNAR2) expression correlates significantly with clinical response to interferon (IFN)-alpha/5-fluorouracil (5-FU) combination therapy for hepatocellular carcinoma (HCC).
With CTLA-4 Nb16 stimulation, dendritic cell/hepatocellular carcinoma fusion cells (DC/HepG2-FCs) enhanced autologous CD8<sup>+</sup> T cell proliferation and production of IFN-<i>γ</i><i>in vitro</i>, thereby leading to enhanced killing of tumor cells.
These results suggested that K6G potentiated the inhibitory effect of IFN-α on HCC cell proliferation through activation of the JAK/STAT signaling pathway by inhibiting SOCS3 expression.
In the case of hepatitis C virus (HCV) infection, important characteristics are nonresponsiveness to IFN therapy and development of hepatocellular carcinoma.
Treating with anti-HN neutralizing mAb induced significant decline in the cytotoxicity of IFN R<sup>-/-</sup> NK cells toward Hepa1-6 cell line (P < 0.05).
In this study, we investigated the effects of IFN-λ on autophagy, a cellular process closely related to hepatitis C virus (HCV) infection in human hepatoma Huh7 cells.
The results indicated that miR-146a regulated the sensitivity of HCC cells to the cytotoxic effects of IFN-α through SMAD4, suggesting that this miRNA could be suitable for prediction of the clinical response and potential therapeutic target in HCC patients on IFN-based therapy.
Emodin also sensitized the antiproliferative effect of IFN-α in HeLa cervical carcinoma cells and reduced tumor growth in Huh7 hepatocellular carcinoma-bearing mice.
The aim of the study was to evaluate the potential of IFN regulatory factor-1 (IRF-1) for cytokine gene therapy of HCC using an IRF-1/human estrogen receptor fusion protein (IRF-1hER), which is reversibly activatable by beta-estradiol (E2).
We found that while HBV replication in transfected human hepatoma Huh-7 cell was severely inhibited by IFN-α treatment as reported previously, this inhibition was markedly impaired in the cell in which the expression of IFN-inducible, double-stranded RNA-dependent protein kinase (PKR) was stably and specifically suppressed through RNA-interference.
In summary, our study suggests that HBV precore protein, specifically the p22 form, impedes JAK-STAT signaling to help the virus evade the host innate immune response and, thus, causes resistance to IFN therapy.<b>IMPORTANCE</b> Chronic hepatitis B virus (HBV) infection continues to be a major global health concern, and patients who fail to mount an efficient immune response to clear the virus will develop a life-long chronic infection that can progress to chronic active hepatitis, cirrhosis, and primary hepatocellular carcinoma.
However, we failed to uncover any significant association between other polymorphisms in genes of IL-12 signaling pathway and HCC risk, including <i>IL18</i>-rs1946518 and -rs187238, <i>IFN-γ</i>-rs2430561, <i>IL12A</i>-rs568408, <i>IL12B</i>-rs3212227 and <i>STAT4</i>-rs7574865.
Maintenance therapy with the use of long-term low-dose PEG-IFNα-2a is effective for preventing HCC occurrence irrespective of the IL28B SNP, at least for a subset of CHC patients.
A systematic review was conducted to identify trials about curative treatment combined with or without adjuvant therapies (interferon, IFN; or transarterial chemoembolization, TACE) for HCC.