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:Aclacinomycin enhances the killing effect of allogeneic NK cells on acute myeloid leukemia cells by inducing immunogenic cell death.
Aclacinomycin enhances the killing effect of allogeneic NK cells on acute myeloid leukemia cells by inducing immunogenic cell death.
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这些结果表明,同种异体 NK 细胞在体外经 ACM 刺激后功能反应增强,与含常规 NK 细胞的对照组相比,表现出更优的效应细胞因子产生和细胞毒性。总之,本研究表明,ACM 与同种异体 NK 细胞的联合是一种有前景的抗 AML 治疗策略。
自然杀伤(NK)细胞对感染性疾病和癌症具有自发细胞毒性,在白血病治疗中也发挥重要作用。尽管基于NK细胞的疗法在髓系白血病治疗中取得了成功,但NK同种异体反应性在这些血液系统恶性肿瘤中的潜在应用仍不明确。本研究旨在探讨异体NK细胞联合阿克拉霉素(ACM)是否能增强对急性髓系白血病(AML)细胞系的抗白血病功能,并阐明其潜在机制。
KG-1和HL-60 AML细胞系接受不同处理。检测了不同药物组合对细胞毒性、细胞活力和凋亡状态的影响。
结果显示,ACM(40 nmol/l)与同种异体NK细胞(比例20:1)联合对AML细胞具有显著细胞毒性,并增加AML细胞凋亡,尤其是在治疗72 h后。后续分析显示,联合治疗组中免疫原性细胞死亡(ICD)相关分子钙网蛋白、三磷酸腺苷和高迁移率族蛋白B1的表达,以及NK细胞效应产物穿孔素和颗粒酶B的表达均显著增加。这些发现表明,ACM通过ICD途径增强同种异体NK细胞的抗白血病活性。
KG-1 and HL-60 AML cell lines were subjected to different treatments. The effects of different drug combinations on cytotoxicity, cell viability, and apoptotic status were examined.
The results showed that the combination of ACM (40 nmol/l) and allogeneic NK cells (ratio 20:1) was significantly cytotoxic to AML cells and increased the apoptosis of AML cells, especially after 72 h of treatment. Subsequent analyses revealed that the expression of immunogenic cell death (ICD)-related molecules calreticulin, adenosine triphosphate, and high mobility group box 1, as well as NK cell effector production-perforin and granzyme B-was markedly increased in the combination treatment group. These findings suggest that ACM enhances the anti-leukemic activity of allogeneic NK cells through the ICD pathway. DISCUSSION: These results demonstrated that allogeneic NK cells had enhanced functional responses when stimulated with ACM in vitro , exhibiting superior effector cytokine production and cytotoxicity compared to the control, which contained conventional NK cells. In conclusion, the present study suggested that the combination of ACM and allogeneic NK cells is a promising therapeutic strategy against AML.
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