Cancer Letters

Available online 11 January 2021

Cancer Letters

Highlights

Irreversible electroporation elicits CD8+ T cell immunity in a murine hepatoma model.

The induced immunity is long-lasting and against hepatocellular carcinoma growth.

Irreversible electroporation reduces Treg and PD-1+ T cells in tumors and spleens.

Irreversible electroporation promotes danger-associated molecular patterns release.

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.

Keywords

Local ablation

Liver cancer

Antitumor immunity

Tumor growth

Abbreviations

IRE

irreversible electroporation

RFA

radiofrequency ablation

DAMPs

danger associated molecular patterns

ATP

adenosine 5′-triphosphates

HMGB1

high mobility group box 1

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© 2021 Published by Elsevier B.V.



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