Details

Autor(en) / Beteiligte

• Dai, Zihao
• Wang, Zongren
• Lei, Kai
• Liao, Junbin
• Peng, Zhenwei
• Lin, Manxia
• Liang, Ping
• Yu, Jie
• Peng, Sui
• Chen, Shuling
• Kuang, Ming

Titel

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

Ist Teil von

• Cancer letters, 2021-04, Vol.503, p.1-10

Ort / Verlag

Ireland: Elsevier B.V

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.