The NF-κB1/p50 Subunit Influences the Notch/IL-6-Driven Expansion of Myeloid-Derived Suppressor Cells in Murine T-Cell Acute Lymphoblastic Leukemia Article Swipe
Behnaz Abdollahzadeh
,
Noemi Martina Cantale Aeo
,
Nike Giordano
,
Andrea Orlando
,
Maria Basciani
,
Giovanna Peruzzi
,
Paola Grazioli
,
Isabella Screpanti
,
María Pía Felli
,
Antonio Francesco Campese
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.3390/ijms25189882
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.3390/ijms25189882
T-cell acute lymphoblastic leukemia is an aggressive neoplasia due to hyper-proliferation of lymphoid progenitors and lacking a definitive cure to date. Notch-activating mutations are the most common in driving disease onset and progression, often in combination with sustained activity of NF-κB. Myeloid-derived suppressor cells represent a mixed population of immature progenitors exerting suppression of anti-cancer immune responses in the tumor microenvironment of many malignancies. We recently reported that in a transgenic murine model of Notch3-dependent T-cell acute lymphoblastic leukemia there is an accumulation of myeloid-derived suppressor cells, dependent on both Notch signaling deregulation and IL-6 production inside tumor T-cells. However, possible interaction between NF-κB and Notch in this context remains unexplored. Interestingly, we also reported that Notch3 transgenic and NF-κB1/p50 deleted double mutant mice display massive myeloproliferation. Here, we demonstrated that the absence of the p50 subunit in these mice dramatically enhances the induction and suppressive function of myeloid-derived suppressor cells. This runs in parallel with an impressive increase in IL-6 concentration in the peripheral blood serum, depending on IL-6 hyper-production by tumor T-cells from double mutant mice. Mechanistically, IL-6 increase relies on loss of the negative control exerted by the p50 subunit on the IL-6 promoter. Our results reveal the Notch/NF-κB cross-talk in regulating myeloid-derived suppressor cell biology in T-cell leukemia, highlighting the need to consider carefully the pleiotropic effects of NF-κB-based therapy on the tumor microenvironment.
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- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/ijms25189882
- OA Status
- gold
- References
- 74
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4402526687
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- OpenAlex ID
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https://openalex.org/W4402526687Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/ijms25189882Digital Object Identifier
- Title
-
The NF-κB1/p50 Subunit Influences the Notch/IL-6-Driven Expansion of Myeloid-Derived Suppressor Cells in Murine T-Cell Acute Lymphoblastic LeukemiaWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
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2024-09-13Full publication date if available
- Authors
-
Behnaz Abdollahzadeh, Noemi Martina Cantale Aeo, Nike Giordano, Andrea Orlando, Maria Basciani, Giovanna Peruzzi, Paola Grazioli, Isabella Screpanti, María Pía Felli, Antonio Francesco CampeseList of authors in order
- Landing page
-
https://doi.org/10.3390/ijms25189882Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.3390/ijms25189882Direct OA link when available
- Concepts
-
Myeloid-derived Suppressor Cell, Cancer research, Biology, Myeloid, Progenitor cell, T cell, Tumor microenvironment, Immunology, Myeloid leukemia, Immune system, Population, Stem cell, Cell biology, Suppressor, Cancer, Medicine, Genetics, Environmental healthTop concepts (fields/topics) attached by OpenAlex
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10Other works algorithmically related by OpenAlex
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| referenced_works | https://openalex.org/W3209215833, https://openalex.org/W2977849918, https://openalex.org/W3108884932, https://openalex.org/W4365448305, https://openalex.org/W4313889569, https://openalex.org/W2884975374, https://openalex.org/W4399032659, https://openalex.org/W3036108906, https://openalex.org/W3111998801, https://openalex.org/W3153827978, https://openalex.org/W2000589976, https://openalex.org/W2055708024, https://openalex.org/W2346775209, https://openalex.org/W2761492606, https://openalex.org/W2179830620, https://openalex.org/W2909318220, https://openalex.org/W2984931754, https://openalex.org/W4401778528, https://openalex.org/W2580215615, https://openalex.org/W4315650759, https://openalex.org/W2018527149, https://openalex.org/W2133440148, https://openalex.org/W2170400030, https://openalex.org/W2108822341, https://openalex.org/W2742440435, https://openalex.org/W2912748266, https://openalex.org/W4206063936, https://openalex.org/W4399880946, https://openalex.org/W1576745000, https://openalex.org/W2884269808, https://openalex.org/W2954714050, https://openalex.org/W4380052535, https://openalex.org/W1859056059, https://openalex.org/W2606083508, https://openalex.org/W3141512116, https://openalex.org/W2471500324, https://openalex.org/W4390673205, https://openalex.org/W4394758930, https://openalex.org/W4304172428, https://openalex.org/W4225511812, https://openalex.org/W2574819148, https://openalex.org/W1988924112, https://openalex.org/W2782630985, https://openalex.org/W3029098010, https://openalex.org/W2032095580, https://openalex.org/W2126247355, https://openalex.org/W3007858510, https://openalex.org/W4392343318, https://openalex.org/W3015047481, https://openalex.org/W2039183048, https://openalex.org/W2010204335, https://openalex.org/W2314890833, https://openalex.org/W4391967991, https://openalex.org/W3014673155, https://openalex.org/W2950397474, https://openalex.org/W4378213792, https://openalex.org/W3128976466, https://openalex.org/W3109289585, https://openalex.org/W2125764628, https://openalex.org/W6822054205, https://openalex.org/W1995124863, https://openalex.org/W2002753637, https://openalex.org/W2063504670, https://openalex.org/W2736259238, https://openalex.org/W2156456343, https://openalex.org/W2129322992, https://openalex.org/W3108832674, https://openalex.org/W2068854551, https://openalex.org/W2160943316, https://openalex.org/W2895851852, https://openalex.org/W2888749522, https://openalex.org/W2035616122, https://openalex.org/W2133982451, https://openalex.org/W4239948248 |
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