AUTHOR=De Re Valli , Rossetto Anna , Rosignoli Alessandro , Muraro Elena , Racanelli Vito , Tornesello Maria Lina , Zompicchiatti Aron , Uzzau Alessandro TITLE=Hepatocellular Carcinoma Intrinsic Cell Death Regulates Immune Response and Prognosis JOURNAL=Frontiers in Oncology VOLUME=12 YEAR=2022 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.897703 DOI=10.3389/fonc.2022.897703 ISSN=2234-943X ABSTRACT=

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.