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:Myeloid-Derived Suppressor Cells in Cancer and COVID-19 as Associated with Oxidative Stress.
Myeloid-Derived Suppressor Cells in Cancer and COVID-19 as Associated with Oxidative Stress.
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髓源性抑制细胞MDSCs是一类异质性细胞群体,在癌症、炎症、细菌和病毒感染等病理状态下会突破其生理调控范围而扩增。其关键特征是具有显著抑制T细胞和自然杀伤NK细胞应答的能力。某些重症COVID-19疾病的危险因素,如肥胖和糖尿病,与氧化应激相关。由此产生的炎症和氧化应激可对宿主产生负面影响。同样,癌细胞表现出内在ROS生成的持续增加,从而维持致癌表型并推动肿瘤进展。通过破坏内质网钙通道,细胞内ROS积累可扰乱蛋白质折叠,并最终导致蛋白质稳态失败。在癌症和COVID-19中,MDSCs由相同的两种亚型组成(PMN-MSDC和M-MDSC)。多形核MDSCs的主要作用是抑制T细胞和NK杀伤细胞的应答,同时它们也产生活性氧ROS和活性氮RNS。我们在此综述MDSCs的来源、其扩增机制,以及在癌症和COVID-19背景下与超氧阴离子•O2-和活性氧ROS存在相关的抑制功能。
Myeloid-derived suppressor cells MDSCs are a heterogeneous population of cells that expand beyond their physiological regulation during pathologies such as cancer, inflammation, bacterial, and viral infections. Their key feature is their remarkable ability to suppress T cell and natural killer NK cell responses. Certain risk factors for severe COVID-19 disease, such as obesity and diabetes, are associated with oxidative stress. The resulting inflammation and oxidative stress can negatively impact the host.
Similarly, cancer cells exhibit a sustained increase in intrinsic ROS generation that maintains the oncogenic phenotype and drives tumor progression. By disrupting endoplasmic reticulum calcium channels, intracellular ROS accumulation can disrupt protein folding and ultimately lead to proteostasis failure.
In cancer and COVID-19, MDSCs consist of the same two subtypes (PMN-MSDC and M-MDSC). While the main role of polymorphonuclear MDSCs is to dampen the response of T cells and NK killer cells, they also produce reactive oxygen species ROS and reactive nitrogen species RNS.
We here review the origin of MDSCs, their expansion mechanisms, and their suppressive functions in the context of cancer and COVID-19 associated with the presence of superoxide anion • O 2 - and reactive oxygen species ROS.
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