Cytarabine‐induced TNFα promotes the expansion and suppressive functions of myeloid‐derived suppressor cells in acute myeloid leukaemia
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Le résumé fourni par la source
Acute myeloid leukaemia (AML) is very common haematopoietic malignancies with poor prognosis. Chemotherapy is still a mainstay therapy for AML patients. AML microenvironment plays critical roles in therapy response. However, the role of chemotherapy in AML microenvironment is poorly understood. In this study, we report that cytarabine (AraC)-triggered TNFα from AML cells expanded myeloid-derived suppressor cells (MDSCs) and enhanced MDSC functions and survival through activating IL-6/STAT3 and NFκB pathways. Blockade of TNFα in conditioned medium-derived AraC-treated AML cells (AraC_CM) impaired MDSC expansion and functions, reduced IL-6 secretion and the level of activated STAT3. Inhibiting IL6 or STAT3 abrogated AraC_CM-mediated MDSC suppressive function. Additionally, inhibiting TNFα also impaired AraC_CM-mediated NFκB activation. Blocking NFκB activation reduced MDSC viability induced by AraC_CM. Together, these results provided a role of AraC-induced TNFα in MDSC expansion and functions and suggest that targeting TNFα may benefit AML patients to current anticancer strategies by blocking MDSC-mediated immunosuppression.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Cytarabine‐induced TNFα promotes the expansion and suppressive functions of myeloid‐derived suppressor cells in acute myeloid leukaemia
- Date Crossref
- 20/03/2022
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Guiyang Medical University pays non établi dans la noticeUniversité ou école supérieure
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Affiliated Hospital of Guizhou Medical University Medical Laboratory Center pays non établi dans la noticeÉtablissement de santé
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Key Laboratory of Medical Molecular Biology of Guizhou Province School of Basic Medical Science Guizhou Medical University Guiyang China Key Laboratory of Endemic and Ethnic Diseases Ministry of Education & pays non établi dans la noticeUniversité ou école supérieure
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Department of Pathophysiology Guizhou Medical University Guiyang China pays non établi dans la noticeUniversité ou école supérieure
Guiyang Medical University, Medical Laboratory Center — Affiliated Hospital of Guizhou Medical University et Key Laboratory of Endemic and Ethnic Diseases Ministry of Education & — Key Laboratory of Medical Molecular Biology of Guizhou Province School of Basic Medical Science Guizhou Medical University Guiyang China, avec 1 autre affiliation.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.