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:Natural killer cell dysfunction is associated with colorectal cancer with severe COVID-19.
Natural killer cell dysfunction is associated with colorectal cancer with severe COVID-19.
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CRC+ 与较低的外周 NK 细胞水平和受损的自然细胞毒性相关,促进了重症 COVID-19 的免疫发病机制,而非免疫控制。
严重急性呼吸综合征冠状病毒2型引起的2019冠状病毒病(COVID-19)给全球公共卫生带来重大挑战,也增加了结直肠癌(CRC)患者的易感性。自然杀伤(NK)细胞是宿主先天免疫系统的第一道防线,可发挥天然杀伤作用并介导针对肿瘤和病毒的细胞毒性。因此,更深入了解NK细胞细胞毒作用可能有助于制定治疗COVID-19相关CRC的策略。
研究CRC合并重症COVID-19(CRC⁺)患者外周NK细胞的细胞毒杀伤功能。
采用流式细胞术分析CRC⁺患者及年龄匹配的CRC患者循环NK和NKT细胞比例。采用实时细胞分析仪评估外周血单个核细胞的NK细胞细胞毒活性(NKCA)及相应NK细胞毒性因子(NKCF)活性。
CRC⁺患者外周NK和NKT细胞数量及比例低于单纯CRC患者。此外,与CRC患者相比,CRC⁺患者对裂解K562细胞的NKCA和NKCF活性更低。在CRC⁺患者中,NKCA与NK细胞数量、NK细胞比例及NKCF活性均呈正相关;NKCF活性也与NK细胞比例呈正相关。此外,CRC患者中NKCA与COVID-19严重程度呈负相关。NKCA的受试者工作特征曲线下面积高于其他指标。
CRC⁺与外周NK细胞减少及天然细胞毒作用受损相关,可能促成重症COVID-19的免疫病理,而非发挥免疫控制作用。
Severe acute respiratory syndrome coronavirus 2 induced coronavirus disease 2019 (COVID-19) has posed a great challenge to public health worldwide and also increased susceptibility to colorectal cancer (CRC). Natural killer (NK) cells serve as the first line of defense in the host's innate immune system, performing natural killing functions and mediating cytotoxicity against tumors and viruses. Therefore, a better understanding of NK cell cytotoxicity may facilitate the development of treatment strategies for CRC-associated with COVID-19. AIM: To investigate the cytotoxic killing function of peripheral NK cells in patients with CRC and severe COVID-19 (CRC + patients).
The percentages of circulating NK and NKT cells in CRC + and age-matched patients with CRC were analyzed using flow cytometry. NK cell cytotoxic activity (NKCA) and corresponding NK cytotoxic factor (NKCF) activity in peripheral blood mononuclear cells were evaluated using a Real-Time Cell Analyzer.
The numbers and percentage of peripheral NK and NKT cells in patients with CRC + were lower than those in patients with CRC. Additionally, compared to patients with CRC, those with CRC + had lower levels of NKCA and NKCF activity in lysed K562 cells. Positive correlations were observed between NKCA and NK cell numbers, NKCA and NK cell percentages, NKCF activity, and NK cell percentages in patients with CRC + . Furthermore, a negative correlation was observed between NKCA and the severity of COVID-19 in patients with CRC. The area under the receiver operating characteristic curve for NKCA was greater than those for the other indices.
CRC + is associated with lower levels of peripheral NK cells and impaired natural cytotoxicity, contributing to the immunopathogenesis of severe COVID-19 rather than immune control.
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