Irreversible electroporation synergizes with oncolytic virus enhances the infiltration of cytotoxic T lymphocytes in the tumor immune microenvironment: a leap from focal therapy to immunotherapy for prostate cancer.

Irreversible electroporation (IRE), a non-thermal focal therapy, employs high-frequency electrical pulses to create tumor cell membrane nanopores, inducing immunogenic cell death. By triggering damage-associated molecular patterns, IRE activates dendritic cells (DCs) to prime systemic cytotoxic T lymphocyte (CTL) responses. However, IRE-activated CTLs predominantly accumulate in perivascular regions, limiting their infiltration into the tumor parenchyma. Oncolytic viruses (OVs) complement IRE by converting the "primed" but spatially restricted CTL response into a robust, intratumoral immune attack. OVs secrete pro-inflammatory chemokines to chemoattract CTLs into the tumor core, while the non-thermal nature of IRE preserves antigen stability and vascular integrity, collectively sustaining DC activation and CTL infiltration. Moreover, intraoperative ultrasound-guided IRE not only establishes physical channels for precise OVs delivery but also enhances tumor cell susceptibility to OVs by disrupting membrane integrity. By bridging focal ablation with adaptive immunity, the synergistic effect-IRE for systemic CTL priming and OVs for localized immune amplification-transforms residual tumors into immunogenic niches, counteracting post-IRE recurrence through durable CTL-mediated clearance. The strategy leverages IRE's functional preservation and OVs' targeted lytic activity to synergistically enhance therapeutic efficacy while minimizing invasiveness.