Irreversible electroporation induces CD8+ T cell immune response against post-ablation hepatocellular carcinoma growth.

Abstract

Ablative treatment evokes antitumor immunity, but knowledge on the emerging irreversible electroporation (IRE)-induced immunity in hepatocellular carcinoma (HCC) is limited. To investigate the immune effects induced by IRE and its role in preventing post-ablation HCC progression, a C57BL/6J mouse model bearing subcutaneous H22 hepatoma was employed. IRE treatment significantly suppresses HCC growth, and treated mice are tumor-free after secondary tumor injection and show increased splenic interferon-gamma (IFN-γ)+CD8+ T cells. Additionally, more CD8+ T and dendritic cells, but not CD4+ T, B or NK cells, infiltrate into peri-ablation zones after IRE at day 7. Depletion of CD8+ T cells induces local tumor regrowth and distant metastasis after IRE. Vaccination using IRE-processed H22 lysates prevents tumorigenesis in mice, suggesting a protective immune response. IRE also alleviates immunosuppression by reducing local and splenic Treg and PD-1+ T cells. Regarding mechanism, IRE induces cell necrosis and significant release of danger-associated molecular patterns including ATP, high mobility group box 1 and calreticulin that are pivotal to CD8+ T cell immunity. Together, IRE is a promising approach to evoke CD8+ T cell immunity, which help prevent post-ablation HCC progression.

• Authors: Zihao Dai, Zongren Wang, Kai Lei, Junbin Liao, Zhenwei Peng, Manxia Lin, Ping Liang, Jie Yu, Sui Peng, Shuling Chen, Ming Kuang
• Journal: Cancer letters (Cancer Lett) Vol. 503 Pg. 1-10 (04 10 2021) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 33444692 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Interferon-gamma

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology)
• Carcinoma, Hepatocellular (immunology, pathology, therapy)
• Cell Line, Tumor
• Dendritic Cells (immunology)
• Disease Progression
• Electroporation
• Hep G2 Cells
• Humans
• Interferon-gamma (metabolism)
• Liver Neoplasms (immunology, pathology, therapy)
• Mice
• Mice, Inbred C57BL
• Radiofrequency Ablation (methods)
• Spleen (immunology)
• Xenograft Model Antitumor Assays