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:Roles of natural killer cells in immunity to cancer, and applications to immunotherapy.
Roles of natural killer cells in immunity to cancer, and applications to immunotherapy.
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近年来,在理解自然杀伤(NK)细胞在抗肿瘤和抗病毒免疫中的作用方面取得了巨大进展。NK细胞是细胞毒性先天淋巴细胞,可产生炎性细胞因子和趋化因子。通过裂解转化或感染的细胞,它们限制肿瘤生长和病毒感染。T细胞识别由MHC分子呈递的肽,而NK细胞则表达识别癌细胞上应激诱导的自体蛋白的受体。同时,其功能活性受到此类细胞上显示的MHC分子的抑制。NK细胞在癌症免疫治疗中的巨大潜力体现在它们能广泛识别应激细胞而不论新抗原呈递如何,并且对因获得性耐药机制而丧失MHC I类表达的肿瘤具有增强的活性。因此,目前有许多努力正在进行中,旨在通过治疗药物动员内源性NK细胞,或提供体外扩增的NK细胞群体作为细胞治疗,在某些情况下通过为NK细胞装备嵌合抗原受体。在此,我们探讨了NK细胞为何正成为癌症治疗武器库中重要新成员的关键特征。
Great strides have been made in recent years towards understanding the roles of natural killer (NK) cells in immunity to tumours and viruses. NK cells are cytotoxic innate lymphoid cells that produce inflammatory cytokines and chemokines. By lysing transformed or infected cells, they limit tumour growth and viral infections. Whereas T cells recognize peptides presented by MHC molecules, NK cells display receptors that recognize stress-induced autologous proteins on cancer cells. At the same time, their functional activity is inhibited by MHC molecules displayed on such cells.
The enormous potential of NK cells for immunotherapy for cancer is illustrated by their broad recognition of stressed cells regardless of neoantigen presentation, and enhanced activity against tumours that have lost expression of MHC class I owing to acquired resistance mechanisms. As a result, many efforts are under way to mobilize endogenous NK cells with therapeutics, or to provide populations of ex vivo-expanded NK cells as a cellular therapy, in some cases by equipping the NK cells with chimeric antigen receptors.
Here we consider the key features that underlie why NK cells are emerging as important new additions to the cancer therapeutic arsenal.
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