ZEB1 shapes AML immunological niches, suppressing CD8 T cell activity while fostering Th17 cell expansion
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved..
Acute myeloid leukemia (AML) progression is influenced by immune suppression induced by leukemia cells. ZEB1, a critical transcription factor in epithelial-to-mesenchymal transition, demonstrates immune regulatory functions in AML. Silencing ZEB1 in leukemic cells reduces engraftment and extramedullary disease in immune-competent mice, activating CD8 T lymphocytes and limiting Th17 cell expansion. ZEB1 in AML cells directly promotes Th17 cell development that, in turn, creates a self-sustaining loop and a pro-invasive phenotype, favoring transforming growth factor β (TGF-β), interleukin-23 (IL-23), and SOCS2 gene transcription. In bone marrow biopsies from AML patients, immunohistochemistry shows a direct correlation between ZEB1 and Th17. Also, the analysis of ZEB1 expression in larger datasets identifies two distinct AML groups, ZEB1high and ZEB1low, each with specific immunological and molecular traits. ZEB1high patients exhibit increased IL-17, SOCS2, and TGF-β pathways and a negative association with overall survival. This unveils ZEB1's dual role in AML, entwining pro-tumoral and immune regulatory capacities in AML blasts.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2024 |
---|---|
Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
---|---|
Enthalten in: |
Cell reports - 43(2024), 2 vom: 27. Feb., Seite 113794 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Bassani, Barbara [VerfasserIn] |
---|
Links: |
---|
Themen: |
CP: Immunology |
---|
Anmerkungen: |
Date Completed 04.03.2024 Date Revised 05.03.2024 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1016/j.celrep.2024.113794 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM36853748X |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM36853748X | ||
003 | DE-627 | ||
005 | 20240305232405.0 | ||
007 | cr uuu---uuuuu | ||
008 | 240217s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/j.celrep.2024.113794 |2 doi | |
028 | 5 | 2 | |a pubmed24n1317.xml |
035 | |a (DE-627)NLM36853748X | ||
035 | |a (NLM)38363677 | ||
035 | |a (PII)S2211-1247(24)00122-0 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Bassani, Barbara |e verfasserin |4 aut | |
245 | 1 | 0 | |a ZEB1 shapes AML immunological niches, suppressing CD8 T cell activity while fostering Th17 cell expansion |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 04.03.2024 | ||
500 | |a Date Revised 05.03.2024 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. | ||
520 | |a Acute myeloid leukemia (AML) progression is influenced by immune suppression induced by leukemia cells. ZEB1, a critical transcription factor in epithelial-to-mesenchymal transition, demonstrates immune regulatory functions in AML. Silencing ZEB1 in leukemic cells reduces engraftment and extramedullary disease in immune-competent mice, activating CD8 T lymphocytes and limiting Th17 cell expansion. ZEB1 in AML cells directly promotes Th17 cell development that, in turn, creates a self-sustaining loop and a pro-invasive phenotype, favoring transforming growth factor β (TGF-β), interleukin-23 (IL-23), and SOCS2 gene transcription. In bone marrow biopsies from AML patients, immunohistochemistry shows a direct correlation between ZEB1 and Th17. Also, the analysis of ZEB1 expression in larger datasets identifies two distinct AML groups, ZEB1high and ZEB1low, each with specific immunological and molecular traits. ZEB1high patients exhibit increased IL-17, SOCS2, and TGF-β pathways and a negative association with overall survival. This unveils ZEB1's dual role in AML, entwining pro-tumoral and immune regulatory capacities in AML blasts | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a CP: Immunology | |
650 | 4 | |a Th17 | |
650 | 4 | |a immune suppression | |
650 | 4 | |a leukemia | |
650 | 4 | |a microenvironment | |
650 | 7 | |a Transforming Growth Factor beta |2 NLM | |
650 | 7 | |a ZEB1 protein, human |2 NLM | |
650 | 7 | |a Zinc Finger E-box-Binding Homeobox 1 |2 NLM | |
650 | 7 | |a ZEB1 protein, mouse |2 NLM | |
700 | 1 | |a Simonetti, Giorgia |e verfasserin |4 aut | |
700 | 1 | |a Cancila, Valeria |e verfasserin |4 aut | |
700 | 1 | |a Fiorino, Antonio |e verfasserin |4 aut | |
700 | 1 | |a Ciciarello, Marilena |e verfasserin |4 aut | |
700 | 1 | |a Piva, Annamaria |e verfasserin |4 aut | |
700 | 1 | |a Khorasani, Arman Mandegar |e verfasserin |4 aut | |
700 | 1 | |a Chiodoni, Claudia |e verfasserin |4 aut | |
700 | 1 | |a Lecis, Daniele |e verfasserin |4 aut | |
700 | 1 | |a Gulino, Alessandro |e verfasserin |4 aut | |
700 | 1 | |a Fonzi, Eugenio |e verfasserin |4 aut | |
700 | 1 | |a Botti, Laura |e verfasserin |4 aut | |
700 | 1 | |a Portararo, Paola |e verfasserin |4 aut | |
700 | 1 | |a Costanza, Massimo |e verfasserin |4 aut | |
700 | 1 | |a Brambilla, Marta |e verfasserin |4 aut | |
700 | 1 | |a Colombo, Giorgia |e verfasserin |4 aut | |
700 | 1 | |a Schwaller, Juerg |e verfasserin |4 aut | |
700 | 1 | |a Tzankov, Alexandar |e verfasserin |4 aut | |
700 | 1 | |a Ponzoni, Maurilio |e verfasserin |4 aut | |
700 | 1 | |a Ciceri, Fabio |e verfasserin |4 aut | |
700 | 1 | |a Bolli, Niccolò |e verfasserin |4 aut | |
700 | 1 | |a Curti, Antonio |e verfasserin |4 aut | |
700 | 1 | |a Tripodo, Claudio |e verfasserin |4 aut | |
700 | 1 | |a Colombo, Mario P |e verfasserin |4 aut | |
700 | 1 | |a Sangaletti, Sabina |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Cell reports |d 2012 |g 43(2024), 2 vom: 27. Feb., Seite 113794 |w (DE-627)NLM217067492 |x 2211-1247 |7 nnns |
773 | 1 | 8 | |g volume:43 |g year:2024 |g number:2 |g day:27 |g month:02 |g pages:113794 |
856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.celrep.2024.113794 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 43 |j 2024 |e 2 |b 27 |c 02 |h 113794 |