Irreversible electroporation activates the NLRP3 inflammasome pathway mediating the antitumor immune responses in pancreatic cancer

This is the authors' abstract. We don't add key points for this paper.

Irreversible electroporation (IRE) become a superior ablation modality for pancreatic cancer (PC) treatment because of its "non-heat"-dependent properties and its immune activation effects. However, the characteristics and mechanisms behind IRE-induced immune responses were poorly understood. In this study, the subtypes of immune cells in orthotopic PC mice treated with IRE were detected using flow cytometry and multiple immunofluorescent staining techniques. Bilateral subcutaneous tumors and in vitro effector-target cell models were used to investigate the antitumor efficacy and characteristics of the IRE-induced immune response. We found that IRE ablation on orthotopic PC resulted in the maximum infiltration of T lymphocytes in PC after 72 h. IRE promotes the transformation of immune cells into an antitumor phenotype and facilitates the infiltration of immune cells into tumor tissues. Additionally, IRE-induced immune response has an antitumor effect, and it can also inhibit the growth of other types of tumors (melanoma and colon cancer). Mechanistically, IRE-induced cell injury triggers the release of damage-associated molecular patterns, which in turn increases the release of pro-inflammatory cytokines IL-1β and IL-18 by activating the NLRP3 inflammasome pathway. IRE ablation on PC can trigger the antitumor immune response by activating the NLRP3 inflammasome pathway, but without rigorous specificity.