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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F23%3A00571076" target="_blank" >RIV/68378050:_____/23:00571076 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388971:_____/23:00571076 RIV/00216208:11130/23:10458307 RIV/00216208:11110/23:10458307 RIV/00216208:11140/23:10458307 a 3 dalších

Výsledek na webu

<a href="https://www.nature.com/articles/s41419-023-05728-w" target="_blank" >https://www.nature.com/articles/s41419-023-05728-w</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41419-023-05728-w" target="_blank" >10.1038/s41419-023-05728-w</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cell Death & Disease

ISSN

2041-4889

e-ISSN

2041-4889

Svazek periodika

14

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

12

Strana od-do

209

Kód UT WoS článku

000958731000002

EID výsledku v databázi Scopus

2-s2.0-85150979168