20.500.12556/RUL-176027 Cytokine-armed pyroptosis induces antitumor immunity against diverse types of tumors Inflammasomes are defense complexes that utilize cytokines and immunogenic cell death (ICD) to stimulate the immune system against pathogens. Inspired by their dual action, we present cytokine-armed pyroptosis as a strategy for boosting immune response against diverse types of tumors. To induce pyroptosis, we utilize designed tightly regulated gasdermin D variants comprising different pore-forming capabilities and diverse modes of activation, representing a toolbox of ICD inducers. We demonstrate that the electrogenic transfer of ICD effector-encoding plasmids into mouse melanoma tumors when combined with intratumoral expression of cytokines IL-1β, IL-12, or IL-18, enhanced anti-tumor immune responses. Careful selection of immunostimulatory molecules is, however, imperative as a combination of IL-1β and IL-18 antagonized the protective effect of pyroptosis by IFNγ-mediated upregulation of several immunosuppressive pathways. Additionally, we show that the intratumoral introduction of armed pyroptosis provides protection against distant tumors and proves effective across various tumor types without inducing systemic inflammation. Deconstructed inflammasomes thus serve as a powerful, tunable, and tumor-agnostic strategy to enhance antitumor response, even against the most resilient types of tumors. cancer immunotherapy NOD-like receptors biokemija imunski odziv tumorji inflamasomi true false true Angleški jezik Slovenski jezik Članek v reviji 2025-11-18 15:27:25 2025-11-18 15:27:26 2025-12-17 03:59:43 0000-00-00 00:00:00 2024 0 0 22 str. art. 10801 Vol. 15 2024 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 0000-00-00 577 2041-1723 10.1038/s41467-024-55083-3 221013763 RAZ_Orehek_Sara_2024.pdf RAZ_Orehek_Sara_2024.pdf 1 F7BD5C5E6975C448294CBB2AB699BB0C 8d25aa1656b0f1fca3101950baab1f2ff96b22fc5306b8fc87c22a80f7219630 5e92df0b-c48a-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=222076 https://www.nature.com/articles/s41467-024-55083-3 0 98623188-c48a-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=222077 Medicinska fakulteta Biotehniška fakulteta 0 0 0