Leveraging the Immunological Impacts of Irreversible Electroporation as a New Frontier for Cancer Therapy

Abstract

Irreversible electroporation (IRE) is a nonthermally mediated tissue ablation modality that makes use of short pulsed electric fields to destroy cancerous lesions in situ. In the past two decades, IRE has established itself not only as an effective means to ablate small, unresectable tumor masses but also as a tool particularly qualified to modulate the tumor microenvironment in a way that dismantles pathways of cancer immunosuppression and permits the development of a systemic antitumor immune response. However, despite its immune-stimulating tendencies, for most cancers conventional IRE alone is insufficient to establish an immune response robust enough to fully eliminate disseminated disease and prevent recurrence. Here, we describe the current understanding of the histological and immunological effects of IRE, as well as recent efforts to optimize IRE parameters and develop rational combination therapies to increase the efficacy of the resulting immune response.

Keywords: H-FIRE; high-frequency irreversible electroporation; immunogenic cell death; in situ cancer vaccination; irreversible electroporation; nanosecond pulsed electric field; nsPEF; tumor microenvironment.