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:The effects of bone marrow humoral components of B-cell acute lymphoblastic leukemia patients on natural killer cell suppression.
The effects of bone marrow humoral components of B-cell acute lymphoblastic leukemia patients on natural killer cell suppression.
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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常规治疗得以存活,但化疗药物具有不良反应,且即使完全康复后复发的可能性仍然存在。鉴于NK细胞在抗癌免疫中的关键作用,探索NK细胞在免疫治疗中潜力的研究激增,这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显著,这提示存在影响NK细胞在给予白血病患者后功能的外部条件。在本研究中,探讨了B-ALL患者骨髓体液成分对健康NK细胞的影响。健康外周血单个核细胞在有和无B-ALL患者骨髓来源血浆样本的条件下进行培养。发现在B-ALL血浆样本存在时,PD-1和IL-10的表达增加,而NK细胞的增殖能力下降。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细胞功能产生抑制作用。
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.
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