ZEB1 shapes AML immunological niches suppressing CD8 T-cell activity while fostering Th17 cell expansion
ABSTRACT Acute myeloid leukemia (AML) development and progression is favored by immune suppression directly triggered by leukemia cells. ZEB1 is a key transcription factor in epithelial-to-mesenchymal transition which, we show here, is capable immune regulation in AML. Leukemic cells which had ZEB1 knocked down have reduced engraftment and extramedullary disease when transplanted into immune competent mice due to concomitant activation of CD8 T lymphocytes and reduced expansion of Th17 cells. Differently, in ZEB1 competent AML, IL-17 sustains the development of a pro-invasive and self-maintaining loop inducingMMPsandSOCS2.In humans, AML patients show,in situon bone marrow biopsies, a direct correlation between ZEB1 and Th17 and, in gene expression profile when divided according to the median value ofZEB1expression, a different overall survival and relapse along with the expression of MMPs, SOCS2 and Th17 cells enrichment. Overall, our data shed new light into the role of ZEB1 in AML that entwines both pro-tumoral and immune regulatory capacity in AML blasts..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 29. Apr. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bassani, Barbara [VerfasserIn] |
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| doi: |
10.1101/2023.07.08.548195 |
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| PPN (Katalog-ID): |
XBI040138488 |
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| 520 | |a ABSTRACT Acute myeloid leukemia (AML) development and progression is favored by immune suppression directly triggered by leukemia cells. ZEB1 is a key transcription factor in epithelial-to-mesenchymal transition which, we show here, is capable immune regulation in AML. Leukemic cells which had ZEB1 knocked down have reduced engraftment and extramedullary disease when transplanted into immune competent mice due to concomitant activation of CD8 T lymphocytes and reduced expansion of Th17 cells. Differently, in ZEB1 competent AML, IL-17 sustains the development of a pro-invasive and self-maintaining loop inducingMMPsandSOCS2.In humans, AML patients show,in situon bone marrow biopsies, a direct correlation between ZEB1 and Th17 and, in gene expression profile when divided according to the median value ofZEB1expression, a different overall survival and relapse along with the expression of MMPs, SOCS2 and Th17 cells enrichment. Overall, our data shed new light into the role of ZEB1 in AML that entwines both pro-tumoral and immune regulatory capacity in AML blasts. | ||
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| 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 | |
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| 700 | 1 | |a Ponzoni, Maurilio |e verfasserin |4 aut | |
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