RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Effects of different conditioning regimens on HLA-mismatched microtransplantation and changes in fine immune indices in acute myeloid leukaemia.
Effects of different conditioning regimens on HLA-mismatched microtransplantation and changes in fine immune indices in acute myeloid leukaemia.
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本研究旨在观察不同预处理方案对急性髓系白血病(AML)患者微移植(MST)后精细免疫指标的影响。本文探讨了微移植可能的免疫机制,并描述了更优化的预处理方案。
本研究共纳入2015年8月至2023年10月在兰州大学第二医院接受MST治疗的55例AML患者,并将13例未接受MST而直接接受维持治疗的AML患者作为对照组(C)。MST患者分为含维奈克拉预处理方案组(A)和不含维奈克拉预处理方案组(B)。通过流式细胞术和细胞因子微球阵列分析检测精细免疫指标。观察治疗前后免疫指标的变化,并分析MST组患者的无进展生存期(PFS)和总生存期(OS)。与B组相比,A组患者的PFS和OS更好。MST后Treg细胞比例和IL-2表达水平升高,而TNF-α和IFN-α降低(P < 0.05)。在B组中,总T细胞、CD4 + T细胞和CD4 + /CD8 + T细胞降低;NK细胞和总B细胞升高;IL-17A在MST期间先升高后降低(P < 0.05)。在MST期间,A组和B组之间的总B细胞、IL-4和IFN-γ存在显著差异。
此外,MST组患者与对照组患者在总T细胞、CD4 + T细胞、Treg细胞、IL-17A、IFN-γ和IL-2方面存在显著差异(P < 0.05)。含维奈克拉的MST预处理方案显著改变了精细免疫指标并显示出更好的疗效,值得进一步研究和临床应用。
The aim of this study was to observe the effects of different conditioning regimens on fine immune indices after microtransplantation (MST) in patients with acute myeloid leukaemia (AML). This article discusses the possible immune mechanism of microtransplantation and describes a more optimized conditioning regimen. A total of 55 AML patients who received MST treatment at the Second Hospital of Lanzhou University from August 2015 to October 2023 were included in this study, and 13 AML patients who did not receive MST but directly received the maintenance therapy were included as the control group (C). The MST patients were divided into a conditioning regimen with venetoclax group (A) and a conditioning regimen without venetoclax group (B).
The fine immune indices were detected by flow cytometry and cytometric bead array analysis. Changes in the immune indices before and after treatment were observed, and the progression-free survival (PFS) and overall survival (OS) of patients in the MST group were analysed. Compared with those in Group B, patients in Group A had better PFS and OS.
The proportion of Treg cells and the expression level of IL-2 were increased, while TNF-α and IFN-α were decreased after MST (P < 0. 05). In Group B, total T cells, CD4 + T cells and CD4 + /CD8 + T cells decreased; NK cells and total B cells increased; and IL-17A first increased and then decreased during the MST (P < 0. 05). There were significant differences in total B cells, IL-4 and IFN-γ between Group A and Group B during MST.
Moreover, there were significant differences in total T cells, CD4 + T cells, Treg cells, IL-17A, IFN-γ and IL-2 between the patients in the MST group and those in the control group (P < 0. 05). The MST conditioning regimen containing venetoclax significantly changed the fine immune indices and showed improved efficacy, which is worthy of further study and clinical application.
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