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:Defining the role of natural killer cells in acute myeloid leukemia through the lens of single-cell omics.
Defining the role of natural killer cells in acute myeloid leukemia through the lens of single-cell omics.
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本综述探讨急性髓系白血病(AML)中自然杀伤(NK)细胞功能改变及其对疾病进展和治疗结局的影响。NK细胞是先天免疫的重要效应细胞,可识别并清除恶性细胞。然而在AML中,NK细胞常出现数量和功能缺陷,导致免疫监视受损,促进肿瘤免疫逃逸和疾病进展。综述系统考察单细胞组学技术在AML研究中的应用,以揭示白血病微环境中NK细胞的组学特征和表型分布;其功能障碍表现为抑制性受体上调、活化信号下调、细胞因子环境改变,以及与骨髓生态位中其他细胞的复杂互作。文章进一步将NK细胞功能动态与传统和新兴治疗(包括CAR-NK免疫疗法)联系起来,强调其在疾病监测和预后分层中的潜在作用。综述还讨论AML的NK细胞免疫治疗策略,重点关注调节或工程化NK细胞以增强抗肿瘤免疫的潜力。深入理解AML中NK细胞生物学及调控机制,对开发新型免疫疗法和改善患者预后至关重要。
This review explores the alterations in natural killer (NK) cell function in acute myeloid leukemia (AML) and their implications for disease progression and therapeutic outcomes. As key effectors of innate immunity, NK cells are critical in recognizing and eliminating malignant cells. In AML, however, NK cells frequently exhibit numerical and functional deficiencies, resulting in compromised immunosurveillance that facilitates tumor immune escape and disease advancement.
We systematically examine the application of single-cell omics technologies in AML research to elucidate the omics profiles and phenotypic distribution of NK cells within the leukemic microenvironment, characterizing their dysfunctional state by upregulated inhibitory receptors, downregulated activating signals, an altered cytokine milieu, and complex cellular crosstalk within the bone marrow (BM) niche.
Furthermore, this article correlates functional dynamics of NK cells with conventional and emerging treatments, including CAR-NK immunotherapy, underscoring their potential role in disease monitoring and prognostic stratification.
We also discuss promising NK cell-based immunotherapeutic strategies for AML, emphasizing the potential of modulating or engineering NK cells to enhance antitumor immunity. A deeper understanding of NK cell biology and regulatory mechanisms in AML is essential for developing novel immunotherapies and improving patient prognosis.
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