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Preventive Inhibition of Liver Tumorigenesis by Systemic Activation of Innate Immune Functions

Jin Lee1, Rui Liao2, Gaowei Wang1

  • 1Department of Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.

Cell Reports
|November 16, 2017
PubMed

Insights

Synthetic double-stranded RNA (dsRNA), polyinosinic-polycytidylic acid (pIC), effectively suppressed liver cancer development in mice. This immunostimulatory agent boosts innate immunity, offering potential for early liver cancer prevention.

Area of Science:

  • Hepatology
  • Immunology
  • Oncology

Background:

  • Liver cancer is a leading cause of cancer death globally.
  • Current treatments lack efficient targeted or immune therapies.
  • Hepatocarcinogenesis involves complex cytoplasmic signaling pathways.

Purpose of the Study:

  • To investigate the liver tumor-inhibitory effects of synthetic double-stranded RNA (dsRNA), polyinosinic-polycytidylic acid (pIC).
  • To explore the potential of pIC as a preventive strategy for liver cancer.

Main Methods:

  • Utilized an inducible mouse gene targeting system (Mx1-cre).
  • Administered pIC at the pre-cancer stage in chemically induced and Pten-loss-associated hepatosteatosis models.
  • Assessed tumor suppression and analyzed innate immune responses.

Main Results:

  • pIC robustly suppressed liver tumorigenesis in multiple models.
  • The dsRNA enhanced anti-tumor innate immunity, including cytokine induction and immune cell activation (NK cells, dendritic cells, macrophages).
  • pIC inhibited liver cancer initiation.

Conclusions:

  • Synthetic dsRNA (pIC) demonstrates potent liver tumor-inhibitory effects.
  • pIC acts by boosting innate anti-tumor immune activities.
  • This finding supports the development of pIC-based preventive and early intervention strategies for liver cancer.
Keywords:
dsRNAimmunotherapyinnate immune systemliver cancerliver tumor-initiating cellsmacrophage polarizationpreventive therapy

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