Frontiers in Oncology (Jul 2022)

Hepatocellular Carcinoma Intrinsic Cell Death Regulates Immune Response and Prognosis

  • Valli De Re,
  • Anna Rossetto,
  • Alessandro Rosignoli,
  • Elena Muraro,
  • Vito Racanelli,
  • Maria Lina Tornesello,
  • Aron Zompicchiatti,
  • Alessandro Uzzau

DOI
https://doi.org/10.3389/fonc.2022.897703
Journal volume & issue
Vol. 12

Abstract

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Ablative and locoregional treatment options, such as radiofrequency, ethanol injection, microwave, and cryoablation, as well as irreversible electroporation, are effective therapies for early-stage hepatocellular carcinoma (HCC). Hepatocyte death caused by ablative procedures is known to increase the release of tumor-associated antigen, thus enhancing tumor immunogenicity. In addition, the heat ablative resection induces pyroptotic cell death accompanied by the release of several inflammatory factors and immune-related proteins, including damage-associated molecular patterns (DAMPs), heat shock proteins (HSPs), ficolin 3, ATP, and DNA/RNA, which potentiate the antitumoral immune response. Surgical approaches that enhance tumor necrosis and reduce hypoxia in the residual liver parenchyma have been shown to increase the disease-free survival rate by reducing the host’s immunosuppressive response. Scalpel devices and targeted surgical approach combined with immune-modulating drugs are an interesting and promising area to maximize therapeutic outcomes after HCC ablation.

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