微小RNA(miRNA)被認為是強效的基因表達調節因子，多項研究已揭示了miRNA在急性骨髓性白血病(AML)患者存活方面的預後價值。最近的研究強有力地表明，miRNA可以通過外泌體(EXOs)從癌細胞轉運到受體免疫微環境(IME)細胞中。我們發現AML母細胞釋放的EXOs在CD4和CD8 T細胞中增強了CD3 T細胞凋亡。我們假設存在於EXOs中的miRNA是介導AML T細胞存活變化的關鍵因素。我們發現AML中常見的高表達miRNA miR-24-3p存在於釋放的EXOs中，這表明EXO-miR-24-3p與孤立的AML T細胞中檢測到的增加的miR-24-3p水平相關。這些結果得到了通過體外生成miR-24-3p富集的EXOs的證實，該富集的miR-24-3p-EXOs增加了T細胞的凋亡和miR-24-3p水平。我們還證明，miR-24-3p的過表達增加了T細胞的凋亡，並通過直接靶向DENN/MADD表達，間接改變NF-κB、p-JAK/STAT和p-ERK信號通路，但促進了調節性T細胞(Treg)的發育。這些結果凸顯了AML母細胞通過轉運miR-24-3p的外泌體間接阻礙T細胞功能的機制。總之，通過研究在白血病IME中被單個miRNA調節的信號網絡，我們旨在發現新的非白血病免疫靶點，以挽救T細胞對AML母細胞的強效抗腫瘤功能。視頻摘要。© 2023年 BioMed Central有限公司，Springer Nature的一部分。

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.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.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.© 2023. BioMed Central Ltd., part of Springer Nature.