Type I interferon signaling in malignant blasts contributes to treatment efficacy in AML patients

0571076 - MBÚ 2024 RIV DE eng J - Článek v odborném periodiku
Holíček, P. - Truxová, I. - Raková, J. - Šálek, C. - Hensler, M. - Kovář, Marek - Reiniš, Milan - Mikyšková, Romana - Pasulka, J. - Vošahlíková, Š. - Remešová, H. - Valentová, I. - Lysák, D. - Holubová, M. - Kašpar, Petr - Procházka, Jan - Kašíková, L. - Špíšek, R. - Galluzzi, L. - Fučiková, J.
Type I interferon signaling in malignant blasts contributes to treatment efficacy in AML patients.
Cell Death & Disease. Roč. 14, č. 3 (2023), č. článku 209. ISSN 2041-4889. E-ISSN 2041-4889
Grant CEP: GA MŠMT LM2023036; GA MŠMT LX22NPO5102
Institucionální podpora: RVO:61388971 ; RVO:68378050
Klíčová slova: acute myeloid-leukemia * alpha * cells * metastasis * signature * radiation * rna
Obor OECD: Immunology; Cell biology (UMG-J)
Impakt faktor: 9, rok: 2022
Způsob publikování: Open access
https://www.nature.com/articles/s41419-023-05728-w

While type I interferon (IFN) is best known for its key role against viral infection, accumulating preclinical and clinical data indicate that robust type I IFN production in the tumor microenvironment promotes cancer immunosurveillance and contributes to the efficacy of various antineoplastic agents, notably immunogenic cell death inducers. Here, we report that malignant blasts from patients with acute myeloid leukemia (AML) release type I IFN via a Toll-like receptor 3 (TLR3)-dependent mechanism that is not driven by treatment. While in these patients the ability of type I IFN to stimulate anticancer immune responses was abolished by immunosuppressive mechanisms elicited by malignant blasts, type I IFN turned out to exert direct cytostatic, cytotoxic and chemosensitizing activity in primary AML blasts, leukemic stem cells from AML patients and AML xenograft models. Finally, a genetic signature of type I IFN signaling was found to have independent prognostic value on relapse-free survival and overall survival in a cohort of 132 AML patients. These findings delineate a clinically relevant, therapeutically actionable and prognostically informative mechanism through which type I IFN mediates beneficial effects in patients with AML.
Trvalý link: https://hdl.handle.net/11104/0342383