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B 细胞急性淋巴细胞白血病患者骨髓体液成分对自然杀伤细胞抑制的影响。

The effects of bone marrow humoral components of B-cell acute lymphoblastic leukemia patients on natural killer cell suppression.

作者信息

Tahrali Ilhan, Yucel Esra, Turkkan Emine, Aycicek Ali, Unuvar Aysegul, Cinar Suzan, Deniz Gunnur

机构信息

Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Türkiye.

Department of Pharmaceutical Microbiology, School of Pharmacy, Istanbul Medipol University, Istanbul, Türkiye.

出版信息

Immunol Res. 2025 Jan 14;73(1):31. doi: 10.1007/s12026-024-09577-3.

DOI:10.1007/s12026-024-09577-3
PMID:39808387
Abstract

B-cell acute lymphoblastic leukemia (B-ALL) is the most common form of cancer diagnosed in children. While the majority of patients survive with conventional treatment, chemotherapeutic agents have adverse effects and the potential for relapse persists even after full recovery. Given their pivotal function in anti-cancer immunity, there has been a surge in research exploring the potential of natural killer (NK) cells in immunotherapy, which has emerged as a promising avenue for treating leukemia. Nevertheless, the efficacy of NK cell immunotherapy is less pronounced than expected, which suggests the external conditions that affect NK cell functions after the administration to patients with leukemia. In this study, the effects of humoral components in the bone marrow humoral components of B-ALL patients on healthy NK cells were investigated. Healthy peripheral blood mononuclear cells were cultured with and without bone marrow-derived plasma samples of B-ALL patients. The expression of PD-1 and IL-10 were found to be increased whereas the proliferative capacities of NK cells were found to be decreased at the presence of B-ALL plasma samples. Moreover, high IL-10 versus low IL-18 levels were detected in bone marrow plasma samples of B-ALL patients. These findings indicate that humoral components in the bone marrow of B-ALL patients exert a suppressive effect on NK cell functions.

摘要

B 细胞急性淋巴细胞白血病(B-ALL)是儿童中最常见的癌症形式。虽然大多数患者通过传统治疗得以存活,但化疗药物有副作用,且即使完全康复后仍有复发的可能性。鉴于自然杀伤(NK)细胞在抗癌免疫中的关键作用,探索 NK 细胞在免疫治疗中的潜力的研究激增,免疫治疗已成为治疗白血病的一个有前景的途径。然而,NK 细胞免疫治疗的疗效不如预期,这表明在给白血病患者施用后影响 NK 细胞功能的外部条件。在本研究中,研究了 B-ALL 患者骨髓体液成分中的体液成分对健康 NK 细胞的影响。将健康外周血单个核细胞与有无 B-ALL 患者骨髓来源的血浆样本一起培养。发现在存在 B-ALL 血浆样本的情况下,PD-1 和 IL-10 的表达增加,而 NK 细胞的增殖能力降低。此外,在 B-ALL 患者的骨髓血浆样本中检测到高 IL-10 与低 IL-18 水平。这些发现表明,B-ALL 患者骨髓中的体液成分对 NK 细胞功能发挥抑制作用。

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The effects of bone marrow humoral components of B-cell acute lymphoblastic leukemia patients on natural killer cell suppression.B 细胞急性淋巴细胞白血病患者骨髓体液成分对自然杀伤细胞抑制的影响。
Immunol Res. 2025 Jan 14;73(1):31. doi: 10.1007/s12026-024-09577-3.
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本文引用的文献

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Serum Tumor Necrosis Factor-Alpha Levels in Acute Leukemia and Its Prognostic Significance.急性白血病患者血清肿瘤坏死因子-α水平及其预后意义
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Natural Killer Cells in Myeloid Malignancies: Immune Surveillance, NK Cell Dysfunction, and Pharmacological Opportunities to Bolster the Endogenous NK Cells.髓系恶性肿瘤中的自然杀伤细胞:免疫监视、NK 细胞功能障碍以及增强内源性 NK 细胞的药理学机会
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Current Advances in Immunotherapy for Acute Leukemia: An Overview of Antibody, Chimeric Antigen Receptor, Immune Checkpoint, and Natural Killer.急性白血病免疫治疗的当前进展:抗体、嵌合抗原受体、免疫检查点及自然杀伤细胞概述
Front Oncol. 2019 Sep 19;9:917. doi: 10.3389/fonc.2019.00917. eCollection 2019.
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Structure of the IFNγ receptor complex guides design of biased agonists.IFNγ 受体复合物的结构指导偏激动剂的设计。
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