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

• Published in: Cancer letters 2021-04, Vol.503, p.1-10
• Main Authors: Dai, Zihao, Wang, Zongren, Lei, Kai, Liao, Junbin, Peng, Zhenwei, Lin, Manxia, Liang, Ping, Yu, Jie, Peng, Sui, Chen, Shuling, Kuang, Ming
• Format: Article
• Language: English
• Subjects: Ablation; Antibodies; Antitumor immunity; Calreticulin; CD4 antigen; CD8 antigen; Dendritic cells; Electroporation; Flow cytometry; Hepatocellular carcinoma; Hepatoma; High temperature; Immune response (cell-mediated); Immunosuppression; Laboratory animals; Liver cancer; Local ablation; Lymphocytes; Lymphocytes T; Lysates; Metastases; Metastasis; PD-1 protein; Spleen; Tumor growth; Tumorigenesis; Tumors; Vaccination; γ-Interferon
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2021.01.001

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. •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.