دورية أكاديمية
Acute myeloid leukemia-derived exosomes deliver miR-24-3p to hinder the T-cell immune response through DENN/MADD targeting in the NF-κB signaling pathways
العنوان: | Acute myeloid leukemia-derived exosomes deliver miR-24-3p to hinder the T-cell immune response through DENN/MADD targeting in the NF-κB signaling pathways |
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المؤلفون: | Khalid Otmani, Redouane Rouas, Laurence Lagneaux, Mohammad Krayem, Hugues Duvillier, Mimoune Berehab, Philippe Lewalle |
المصدر: | Cell Communication and Signaling, Vol 21, Iss 1, Pp 1-13 (2023) |
بيانات النشر: | BMC, 2023. |
سنة النشر: | 2023 |
المجموعة: | LCC:Medicine LCC:Cytology |
مصطلحات موضوعية: | AML, miR-24-3p, T cells, Immune response, Apoptosis, Medicine, Cytology, QH573-671 |
الوصف: | Abstract Background microRNAs (miRNAs) are known as potent gene expression regulators, and several studies have revealed the prognostic value of miRNAs in acute myeloid leukemia (AML) patient survival. Recently, strong evidence has indicated that miRNAs can be transported by exosomes (EXOs) from cancer cells to recipient immune microenvironment (IME) cells. Results We found that AML blast-released EXOs enhance CD3 T-cell apoptosis in both CD4 and CD8 T cells. We hypothesized that miRNAs present in EXOs are key players in mediating the changes observed in AML T-cell survival. We found that miR-24-3p, a commonly overexpressed miRNA in AML, was present in released EXOs, suggesting that EXO-miR-24-3p was linked to the increased miR-24-3p levels detected in isolated AML T cells. These results were corroborated by ex vivo-generated miR-24-3p-enriched EXOs, which showed that miR-24-3p-EXOs increased apoptosis and miR-24-3p levels in T cells. We also demonstrated that overexpression of miR-24-3p increased T-cell apoptosis and affected T-cell proliferation by directly targeting DENN/MADD expression and indirectly altering the NF-κB, p-JAK/STAT, and p-ERK signaling pathways but promoting regulatory T-cell (Treg) development. Conclusions These results highlight a mechanism through which AML blasts indirectly impede T-cell function via transferred exosomal miR-24-3p. In conclusion, by characterizing the signaling network regulated by individual miRNAs in the leukemic IME, we aimed to discover new nonleukemic immune targets to rescue the potent antitumor function of T cells against AML blasts. Video Abstract |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1478-811X 69363404 |
Relation: | https://doaj.org/toc/1478-811X |
DOI: | 10.1186/s12964-023-01259-1 |
URL الوصول: | https://doaj.org/article/f4d658a69363404cab167b31bb3e60bc |
رقم الأكسشن: | edsdoj.f4d658a69363404cab167b31bb3e60bc |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 1478811X 69363404 |
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DOI: | 10.1186/s12964-023-01259-1 |