Targeting Tumor‐Associated Antigens in Hepatocellular Carcinoma for Immunotherapy: Past Pitfalls and Future Strategies

Investigators propose a new vaccine platform that enhances all three arms of the adaptive immune system to improve tumor‐associated antigens‐based cancer vaccination in hepatocellular carcinoma patients.
[Hepatology]
Lu, L., Jiang, J., Zhan, M., Zhang, H., Wang, Q.-T., Sun, S.-N., Guo, X.-K., Yin, H., Wei, Y., Li, S.-Y., Liu, J. O., Li, Y., & He, Y.-W. (n.d.). Targeting Tumor-Associated Antigens in Hepatocellular Carcinoma for Immunotherapy: Past Pitfalls and Future Strategies. Hepatology, n/a(n/a). https://doi.org/10.1002/hep.31502 Cite
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Everest Medicines Announces First Patient Dosed in a Phase 1b/2 Study of FGF401 in Combination with Pembrolizumab for the Treatment of Advanced Solid Tumors

Everest Medicines has announced that the first patient has been dosed in a Phase Ib/II study evaluating FGF401 in combination with PD-1 inhibitor, pembrolizumab, in patients with advanced solid tumors, such as hepatocellular carcinoma.
[Everest Medicines]
Press Release

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Tonicity-Responsive Enhancer-Binding Protein Promotes Stemness of Liver Cancer and Cisplatin Resistance

Tonicity-responsive enhancer binding protein (TonEBP) was required for the tumorigenesis and self-renewal of liver CSCs. Cisplatin induced the recruitment of the ERCC1/XPF dimer to the chromatin in a TonEBP-dependent manner leading to DNA repair and cisplatin resistance.
[Ebiomedicine]
Lee, J. H., Suh, J. H., Kang, H. J., Choi, S. Y., Jung, S. W., Lee-Kwon, W., Park, S.-A., Kim, H., Ye, B. J., Yoo, E. J., Jeong, G. W., Park, N. H., & Kwon, H. M. (2020). Tonicity-responsive enhancer-binding protein promotes stemness of liver cancer and cisplatin resistance. EBioMedicine, 58. https://doi.org/10.1016/j.ebiom.2020.102926 Cite
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Selenoprotein P Inhibits Cell Proliferation and ROX Production in HCC Cells

Researchers observed the expression of selenoprotein P in livers from patients with hepatocellular carcinoma (HCC) and explored its effect on HCC cells.
[PLoS One]
Wang, J., Shen, P., Liao, S., Duan, L., Zhu, D., Chen, J., Chen, L., Sun, X., & Duan, Y. (2020). Selenoprotein P inhibits cell proliferation and ROX production in HCC cells. PLOS ONE, 15(7), e0236491. https://doi.org/10.1371/journal.pone.0236491 Cite
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Auranofin Mitigates Systemic Iron Overload and Induces Ferroptosis via Distinct Mechanisms

The authors identified iron modulators by functionally screening hepcidin agonists using a library of 640 FDA-approved drugs in human hepatic Huh7 cells.
[Signal Transduction and Targeted Therapy]
Yang, L., Wang, H., Yang, X., Wu, Q., An, P., Jin, X., Liu, W., Huang, X., Li, Y., Yan, S., Shen, S., Liang, T., Min, J., & Wang, F. (2020). Auranofin mitigates systemic iron overload and induces ferroptosis via distinct mechanisms. Signal Transduction and Targeted Therapy, 5(1), 1–9. https://doi.org/10.1038/s41392-020-00253-0 Cite
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The AKT-Independent MET–V-ATPase–Mtor Axis Suppresses Liver Cancer Vaccination

Scientists investigated the regulatory effect and potential mechanism of hepatocyte growth factor receptor (MET, also known as HGFR) on tumor vaccinations for liver cancer in mice.
[Signal Transduction and Targeted Therapy]
Huang, X., Xu, X., Wang, X., Tang, T., Li, E., Zhang, X., Xu, J., Shen, H., Guo, C., Xu, T., Ren, J., Bai, X., & Liang, T. (2020). The AKT-independent MET–V-ATPase–MTOR axis suppresses liver cancer vaccination. Signal Transduction and Targeted Therapy, 5(1), 1–10. https://doi.org/10.1038/s41392-020-0179-x Cite
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HNF4α Regulates Sulfur Amino Acid Metabolism and Confers Sensitivity to Methionine Restriction in Liver Cancer

The authors report that hepatocyte nuclear factor 4α (HNF4α) dictated the sensitivity of liver cancer to methionine restriction. They showed that hepatic sulfur amino acid metabolism was under transcriptional control of HNF4α.
[Nature Communications]
Xu, Q., Li, Y., Gao, X., Kang, K., Williams, J. G., Tong, L., Liu, J., Ji, M., Deterding, L. J., Tong, X., Locasale, J. W., Li, L., Shats, I., & Li, X. (2020). HNF4α regulates sulfur amino acid metabolism and confers sensitivity to methionine restriction in liver cancer. Nature Communications, 11(1), 3978. https://doi.org/10.1038/s41467-020-17818-w Cite
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Immunological Distinctions between Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma

The objective of this study was to differentiate the roles of specific immune cell subsets in nonalcoholic steatohepatitis and hepatocellular carcinoma pathogenesis.
[Experimental and Molecular Medicine]
Koo, S.-Y., Park, E.-J., & Lee, C.-W. (2020). Immunological distinctions between nonalcoholic steatohepatitis and hepatocellular carcinoma. Experimental & Molecular Medicine, 1–11. https://doi.org/10.1038/s12276-020-0480-3 Cite
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Reduced Mrp2 Surface Availability as PI3Kγ-Mediated Hepatocytic Dysfunction Reflecting a Hallmark of Cholestasis in Sepsis

Keeping the surface availability of the biliary transporter Mrp2 is a cell biological process that may underlie the observation that PI3Kγ loss-of-function protects from hepatic excretory dysfunction during early sepsis
[Scientific Reports]
Beer, A. J., Hertz, D., Seemann, E., Beretta, M., Westermann, M., Bauer, R., Bauer, M., Kessels, M. M., & Qualmann, B. (2020). Reduced Mrp2 surface availability as PI3Kγ-mediated hepatocytic dysfunction reflecting a hallmark of cholestasis in sepsis. Scientific Reports, 10(1), 13110. https://doi.org/10.1038/s41598-020-69901-3 Cite
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LncRNA KCNQ1OT1 Regulates the Invasion and Migration of Hepatocellular Carcinoma by Acting on S1PR1 through miR-149

A xenograft tumour assay was used to validate the role of KCNQ1OT1 in vivo. KCNQ1OT1 and S1PR1 were significantly increased, but miR-149 was decreased in HCC cells.
[Cancer Gene Therapy]
Cheng, J.-L., Li, D.-J., Lv, M.-Y., Pei, Y.-J., Zhang, X.-J., Li, L., Liu, X.-Y., & Fan, A.-H. (2020). LncRNA KCNQ1OT1 regulates the invasion and migration of hepatocellular carcinoma by acting on S1PR1 through miR-149. Cancer Gene Therapy, 1–14. https://doi.org/10.1038/s41417-020-0203-x Cite
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Neohesperidin Enhances PGC-1α-Mediated Mitochondrial Biogenesis and Alleviates Hepatic Steatosis in High Fat Diet Fed Mice

Neohesperidin (NHP) elevated hepatic mitochondrial biogenesis and fatty acid oxidation by increasing PGC-1α expression. The activation of AMP-activated protein kinase was involved in NHP induced PGC-1α expression.
[FASEB Journal]
Wang, S., Sheng, H., Bai, Y., Weng, Y., Fan, X., Lou, L., & Zhang, F. (2020). Neohesperidin enhances PGC-1α-mediated mitochondrial biogenesis and alleviates hepatic steatosis in high fat diet fed mice. Nutrition & Diabetes, 10(1), 1–11. https://doi.org/10.1038/s41387-020-00130-3 Cite
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HGF and IL-10 Expressing ALB::GFP Reporter Cells Generated From iPSCs Show Robust Anti-Fibrotic Property in Acute Fibrotic Liver Model

Induced hepatocyte-like (iHep) cells were generated from induced pluripotent stem cells integrated with the albumin reporter gene. The therapeutic properties of these iHep cells were investigated after transplantation in fibrotic liver tissues of a mouse model.
[Stem Cell Research & Therapy]
Choi, J. S., Jeong, I. S., Park, Y.-J., & Kim, S.-W. (2020). HGF and IL-10 expressing ALB::GFP reporter cells generated from iPSCs show robust anti-fibrotic property in acute fibrotic liver model. Stem Cell Research & Therapy, 11(1), 332. https://doi.org/10.1186/s13287-020-01745-0 Cite
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