ApoA-I/HDL通过抑制AIM2炎性小体活化增强急性髓系白血病CD8+T细胞抗肿瘤活性的机制研究

目前免疫治疗在急性髓系白血病（AML）中的疗效欠佳，主要原因是发挥主要抗肿瘤作用的CD8+T细胞功能紊乱。因此，寻找CD8+T细胞功能紊乱的机制及恢复其功能是免疫治疗发挥作用的关键。前期研究发现，载脂蛋白A-I（ApoA-I）/高密度脂蛋白（HDL）与AML预后及CD8+T细胞比例正相关，HDL处理可增强AML驯化CD8+T细胞的细胞毒功能。ApoA-I/HDL刺激可抑制AML细胞AIM2炎性小体激活，大数据分析亦支持了AIM2炎性小体与AML不良预后及免疫抑制的相关性。为此我们提出：ApoA-I/HDL能否增强CD8+T细胞免疫活性而起抗AML作用？ApoA-I/HDL能否通过抑制AIM2炎性小体活化而增强CD8+T细胞功能？ApoA-I/HDL又是如何抑制AIM2炎性小体？本研究的实施将进一步阐明ApoA-I/HDL对AML中CD8+T细胞功能的调控机制，为其在AML中的应用提供依据。

At present, immunotherapy in acute myeloid leukemia (AML) is less effective, mainly due to the dysfunction of CD8+T cells, which play the main anti-tumor role. Therefore, it is important to reveal the mechanism of CD8+T cell dysfunction and restore its function to improve the therapeutic effect of immunotherapy. We previously found that apolipoprotein A-I (ApoA-I)/high-density lipoprotein (HDL) is positively associated with the proportion of CD8+T cells and improved survival of AML. Moreover, HDL can enhance the cytotoxic function of CD8+T cells acclimated by AML. ApoA-I/HDL stimulation inhibits AIM2 inflammasome activation in AML cells, and the analysis of public RNA-seq data also supports the association of AIM2 inflammasome with poor prognosis and immunosuppression of AML. Therefore, we raised the following scientific questions: Can ApoA-I/HDL enhance the immune activity of CD8+T cells and play an anti-tumor role in AML? Can ApoA-I/HDL enhance CD8+T cell function by inhibiting AIM2 inflammasome activation? How does ApoA-I/HDL inhibit AIM2 inflammasomes? The implementation of this study will further clarify the mechanism of ApoA-I/HDL on the function of CD8+T cells in AML, and provide a scientific evidence for its application in AML.