From local to systemic treatment: Leveraging antitumor immunity following irreversible electroporation

Abstract

Irreversible electroporation (IRE) may result in a form of immunogenic tumor cell death that converts the tumor microenvironment from immune suppressive to immune permissive. The resulting influx of pro-inflammatory innate immune cells and subsequent uptake of apoptotic cell fragments could ultimately result in the priming of tumor-specific killer T cells in the lymph nodes directly draining the tumor ablation site. These T cells in turn will recirculate through peripheral blood and may thus provide systemic protection against the outgrowth of distant metastases. Local tumor ablation through IRE may thus be translated into a systemic antitumor treatment by virtue of secondarily induced T cell priming. These processes may be further facilitated by the primarily nonthermal mechanism of action of IRE, resulting in the conservation of the intra- and peritumoral vasculature and the preserved chemical structure of damage-associated molecular patterns (DAMPs) that are vital for proper immune activation. In this chapter, different clinically explored local tumor ablation techniques are reviewed in relation to their ability to prime or boost an antitumor immune response. Evidence for similar antitumor immune effects of IRE are discussed, as well as ways in which this antitumor immune efficacy may be enhanced through combination treatment with immune modulatory regimens.