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:Empowering Natural Killer Cells to Combat Acute Myeloid Leukemia: Perspective on CAR-NK Cell Therapy.
Empowering Natural Killer Cells to Combat Acute Myeloid Leukemia: Perspective on CAR-NK Cell Therapy.
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在本综述中,我们总结了使用来自不同细胞来源的细胞因子刺激或基因工程改造的 NK 细胞治疗 AML 的临床前研究及其向早期临床试验的转化。我们还概述了近期有望在不久的将来实施的创新性 NK 细胞疗法的进展。
急性髓系白血病(AML)是一种侵袭性血液系统恶性肿瘤,复发率高,治疗选择仍然有限。基于自然杀伤(NK)细胞的免疫治疗有潜力改善AML患者的预后。概述:近期临床前研究和早期临床试验旨在通过嵌合抗原受体(CAR)选择性靶向AML细胞,从而增强NK细胞固有的抗白血病特性。此外,NK细胞和CAR-NK细胞可与其他治疗方式联合使用,或进一步工程化改造,以克服AML原始细胞和白血病起始细胞(LIC)的免疫抑制微环境和治疗耐药性。
BACKGROUND: Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with a high relapse rate and still limited therapeutic options. Natural killer (NK) cell-based immunotherapy has the potential to improve outcomes for patients with AML. SUMMARY: Recent preclinical studies and early-stage clinical trials aim to enhance the intrinsic anti-leukemic properties of NK cells by selectively targeting AML cells with chimeric antigen receptors (CARs). Furthermore, NK and CAR-NK cells can be combined with other therapeutic modalities or engineered further to overcome the immunosuppressive microenvironment, and treatment resistance of AML blasts and leukemia-initiating cells (LIC). KEY MESSAGES: In this review, we summarize preclinical studies with cytokine-stimulated or genetically engineered NK cells derived from different cell sources for the treatment of AML and their translation into early-phase clinical trials. We also provide an overview of promising recent developments toward innovative NK cell-based therapies that may be implemented in the near future.
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