Publication Name	World Journal of Gastroenterology
Manuscript ID	120765
Country	United States

Category	Oncology
Manuscript Type	Correspondence
Article Title	Letter to the Editor: High-frequency irreversible electroporation as an immune primer in hepatocellular carcinoma
Manuscript Source	Invited Manuscript
All Author List	Arunkumar Krishnan and Diptasree Mukherjee
Funding Agency and Grant Number
Corresponding Author	Arunkumar Krishnan, MD, Department of Supportive Oncology, Atrium Health Levine Cancer, Atrium Health Wake Forest Baptist Comprehensive Cancer Center, 1021 Morehead Medical Dr, Charlotte, NC 28204, United States. dr.arunkumar.krishnan@gmail.com
Key Words	High-frequency irreversible electroporation; Hepatocellular carcinoma; Immunogenic cell death; Tumor microenvironment; Programmed death-1; Programmed death-ligand 1; Abscopal effect; Tumor immunotherapy; Liver ablation; Translational oncology
Core Tip	High-frequency irreversible electroporation induces features consistent with immunogenic cell death in hepatocellular carcinoma tumors and, when combined with the small-molecule programmed death (PD)-1/PD-ligand 1 interaction inhibitor BMS-1 and TLR7/8 agonist resiquimod, reverses immunosuppression both locally and systemically. While this triple combination shows strong preclinical efficacy, including a robust abscopal effect, important limitations, such as dependence on a subcutaneous ectopic model, single-timepoint immune profiling, and lack of immune memory validation, need to be addressed before moving to clinical trials. Future research should focus on validating orthotopic models, conducting longitudinal immune studies, performing tumor rechallenge experiments, and optimizing nanoparticle drug delivery as important steps toward a Phase I trial in unresectable hepatocellular carcinoma.
Citation	Krishnan A, Mukherjee D. Letter to the Editor: High-frequency irreversible electroporation as an immune primer in hepatocellular carcinoma. World J Gastroenterol 2026; In press

Received	2026-03-09 06:22
Peer-Review Started	2026-03-09 06:22
First Decision by Editorial Office Director	2026-04-10 09:39
Return for Revision	2026-04-10 09:39
Revised	2026-04-14 13:52
Publication Fee Transferred
Second Decision by Editor	2026-04-24 02:36
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-04-24 09:59
Articles in Press	2026-04-24 09:59
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1007-9327 (print) and 2219-2840 (online)
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