When Electric Fields Become Immune Signals: Electroporation-Driven Antitumor Immunity

Harnessing the destructive force of the immune system against cancer cells in the human body has been achieved through numerous approaches such as immunotherapies, vac-cines, immune checkpoint inhibitors. Unfortunately, these approaches do not always provide the sought-after success, because tumors possess a plethora of evasion methods. Overcoming these barriers is the primary objective of electroporation-based therapies. Electroporation (EP) is a technique that uses high-amplitude, short-duration electric pulses that create temporary or permanent (depending on the strength and duration of the applied electric field) pores within the cell membrane. Beyond physical changes, EP induces immunogenic cell death (ICD) – a type of cell death that is marked by the release of damage-associated molecular patterns (DAMPs). This review explores the cellular and molecular mechanisms through which different EP techniques activate innate and adaptive antitumor immunity, convert immunologically "cold" tumors into "hot" phenotypes and elicit systemic, abscopal immunity.