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:Manipulating NK cellular therapy from cancer to invasive fungal infection: promises and challenges.
Manipulating NK cellular therapy from cancer to invasive fungal infection: promises and challenges.
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侵袭性真菌感染是免疫功能受损患者的重要并发症,治疗选择有限且预后不佳。自然杀伤(NK)细胞是先天免疫系统的重要效应细胞,能够识别并杀伤感染细胞,也可能参与抗真菌防御。本文综述NK细胞过继治疗用于侵袭性真菌感染的研究进展,讨论NK细胞的效应机制、细胞来源与可获得性,以及体外激活和扩增策略。我们还介绍通过基因工程增强NK细胞功能的可能途径,包括嵌合抗原受体(CAR)改造,并探讨将NK细胞治疗开发为免疫受损患者抗真菌治疗手段所面临的机遇与挑战。
The ideal strategy to fight an infection involves both (i) weakening the invading pathogen through conventional antimicrobial therapy, and (ii) strengthening defense through the augmentation of host immunity. This is even more pertinent in the context of invasive fungal infections whereby the majority of patients have altered immunity and are unable to mount an appropriate host response against the pathogen. Natural killer (NK) cells fit the requirement of an efficient, innate executioner of both tumour cells and pathogens - their unique, targeted cell killing mechanism, combined with other arms of the immune system, make them potent effectors.
These characteristics, together with their ready availability (given the various sources of extrinsic NK cells available for harvesting), make NK cells an attractive choice as adoptive cellular therapy against fungi in invasive infections.
Improved techniques in ex vivo NK cell activation with expansion, and more importantly, recent advances in genetic engineering including state-of-the-art chimeric antigen receptor platform development, have presented an opportune moment to harness this novel therapeutic as a key component of a multipronged strategy against invasive fungal infections.
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