Hepatocellular Carcinoma Intrinsic Cell Death Regulates Immune Response and Prognosis

Overview

Journal Front Oncol

Specialty Oncology

Date 2022 Jul 25

PMID 35875093

Authors

Valli De Re

Anna Rossetto

Alessandro Rosignoli

Elena Muraro

Vito Racanelli

Maria Lina Tornesello

Aron Zompicchiatti

Alessandro Uzzau

Affiliations

Soon will be listed here.

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.

Citing Articles

pir-hsa-216911 inhibit pyroptosis in hepatocellular carcinoma by suppressing TLR4 initiated GSDMD activation.

Liao Z, Yang L, Cheng X, Huang X, Zhang Q, Wen D Cell Death Discov. 2025; 11(1):11.

PMID: 39824843 PMC: 11742400. DOI: 10.1038/s41420-024-02285-9.

Current applications of tumor local ablation (TLA) combined with immune checkpoint inhibitors in breast cancer treatment.

Tang L, Wang D, Hu T, Lin X, Wu S Cancer Drug Resist. 2024; 7:33.

PMID: 39403601 PMC: 11472568. DOI: 10.20517/cdr.2024.77.

New insights into mechanisms and interventions of locoregional therapies for hepatocellular carcinoma.

Liu H, Wang C, Wang R, Cao H, Cao Y, Huang T Chin J Cancer Res. 2024; 36(2):167-194.

PMID: 38751435 PMC: 11090796. DOI: 10.21147/j.issn.1000-9604.2024.02.06.

Radiation and Immune Checkpoint Inhibitors: Combination Therapy for Treatment of Hepatocellular Carcinoma.

Chami P, Diab Y, Khalil D, Azhari H, Jarnagin W, Abou-Alfa G Int J Mol Sci. 2023; 24(23).

PMID: 38069095 PMC: 10706661. DOI: 10.3390/ijms242316773.

Efficacy of Αtezolizumab-Βevacizumab in BCLC-C cirrhotic patients with hepatocellular carcinoma according to the type of disease progression, the type of BCLC-C and liver disease severity.

Spyridon P, Antonia S, Dionysia M, Ioanna S, Georgia B, Nikolaos P J Cancer Res Clin Oncol. 2023; 149(11):9253-9261.

PMID: 37199835 DOI: 10.1007/s00432-023-04846-4.

References

Bertheloot D, Latz E, Franklin B . Necroptosis, pyroptosis and apoptosis: an intricate game of cell death. Cell Mol Immunol. 2021; 18(5):1106-1121. PMC: 8008022. DOI: 10.1038/s41423-020-00630-3. View

Nazio F, Bordi M, Cianfanelli V, Locatelli F, Cecconi F . Autophagy and cancer stem cells: molecular mechanisms and therapeutic applications. Cell Death Differ. 2019; 26(4):690-702. PMC: 6460398. DOI: 10.1038/s41418-019-0292-y. View

Guicciardi M, Malhi H, Mott J, Gores G . Apoptosis and necrosis in the liver. Compr Physiol. 2013; 3(2):977-1010. PMC: 3867948. DOI: 10.1002/cphy.c120020. View

Abreu de Carvalho L, Logghe B, Van Cleven S, Vanlander A, Moura Ribeiro S, Geboes K . Local control of hepatocellular carcinoma and colorectal liver metastases after surgical microwave ablation without concomitant hepatectomy. Langenbecks Arch Surg. 2021; 406(8):2749-2757. DOI: 10.1007/s00423-021-02219-4. View

Zhang Q, Lou Y, Bai X, Liang T . Intratumoral heterogeneity of hepatocellular carcinoma: From single-cell to population-based studies. World J Gastroenterol. 2020; 26(26):3720-3736. PMC: 7383842. DOI: 10.3748/wjg.v26.i26.3720. View

Rossetto A, De Re V, Steffan A, Ravaioli M, Miolo G, Leone P . Carcinogenesis and Metastasis in Liver: Cell Physiological Basis. Cancers (Basel). 2019; 11(11). PMC: 6895858. DOI: 10.3390/cancers11111731. View

Sutter O, Calvo J, Nkontchou G, Nault J, Ourabia R, Nahon P . Safety and Efficacy of Irreversible Electroporation for the Treatment of Hepatocellular Carcinoma Not Amenable to Thermal Ablation Techniques: A Retrospective Single-Center Case Series. Radiology. 2017; 284(3):877-886. DOI: 10.1148/radiol.2017161413. View

Rebouissou S, Nault J . Advances in molecular classification and precision oncology in hepatocellular carcinoma. J Hepatol. 2020; 72(2):215-229. DOI: 10.1016/j.jhep.2019.08.017. View

Galluzzi L, Vitale I, Warren S, Adjemian S, Agostinis P, Buque Martinez A . Consensus guidelines for the definition, detection and interpretation of immunogenic cell death. J Immunother Cancer. 2020; 8(1). PMC: 7064135. DOI: 10.1136/jitc-2019-000337. View

10.

Narayanankutty V, Narayanankutty A, Nair A . Heat Shock Proteins (HSPs): A Novel Target for Cancer Metastasis Prevention. Curr Drug Targets. 2018; 20(7):727-737. DOI: 10.2174/1389450120666181211111815. View

11.

Den Brok M, Sutmuller R, van der Voort R, Bennink E, Figdor C, Ruers T . In situ tumor ablation creates an antigen source for the generation of antitumor immunity. Cancer Res. 2004; 64(11):4024-9. DOI: 10.1158/0008-5472.CAN-03-3949. View

12.

Meng Q, Li B, Xiao X . Toward Developing Chemical Modulators of Hsp60 as Potential Therapeutics. Front Mol Biosci. 2018; 5:35. PMC: 5920047. DOI: 10.3389/fmolb.2018.00035. View

13.

Refolo M, Messa C, Guerra V, Carr B, DAlessandro R . Inflammatory Mechanisms of HCC Development. Cancers (Basel). 2020; 12(3). PMC: 7139884. DOI: 10.3390/cancers12030641. View

14.

Lai Q, Iesari S, Finkenstedt A, Hoppe-Lotichius M, Foguenne M, Lehner K . Hepatocellular carcinoma recurrence after acute liver allograft rejection treatment: A multicenter European experience. Hepatobiliary Pancreat Dis Int. 2019; 18(6):517-524. DOI: 10.1016/j.hbpd.2019.05.006. View

15.

Jassey A, Liu C, Changou C, Richardson C, Hsu H, Lin L . Hepatitis C Virus Non-Structural Protein 5A (NS5A) Disrupts Mitochondrial Dynamics and Induces Mitophagy. Cells. 2019; 8(4). PMC: 6523690. DOI: 10.3390/cells8040290. View

16.

David B, Rezende R, Antunes M, Santos M, Freitas Lopes M, Diniz A . Combination of Mass Cytometry and Imaging Analysis Reveals Origin, Location, and Functional Repopulation of Liver Myeloid Cells in Mice. Gastroenterology. 2016; 151(6):1176-1191. DOI: 10.1053/j.gastro.2016.08.024. View

17.

Seror O . Ablative therapies: Advantages and disadvantages of radiofrequency, cryotherapy, microwave and electroporation methods, or how to choose the right method for an individual patient?. Diagn Interv Imaging. 2015; 96(6):617-24. DOI: 10.1016/j.diii.2015.04.007. View

18.

Robinson M, Harmon C, OFarrelly C . Liver immunology and its role in inflammation and homeostasis. Cell Mol Immunol. 2016; 13(3):267-76. PMC: 4856809. DOI: 10.1038/cmi.2016.3. View

19.

Wang K, Wang C, Jiang H, Zhang Y, Lin W, Mo J . Combination of Ablation and Immunotherapy for Hepatocellular Carcinoma: Where We Are and Where to Go. Front Immunol. 2022; 12:792781. PMC: 8714655. DOI: 10.3389/fimmu.2021.792781. View

20.

Guo Y, Xiao Z, Yang L, Gao Y, Zhu Q, Hu L . Hypoxia‑inducible factors in hepatocellular carcinoma (Review). Oncol Rep. 2019; 43(1):3-15. PMC: 6908932. DOI: 10.3892/or.2019.7397. View