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:Driving natural killer cell-based cancer immunotherapy for cancer treatment: An arduous journey to promising ground.
Driving natural killer cell-based cancer immunotherapy for cancer treatment: An arduous journey to promising ground.
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免疫治疗是癌症治疗中最有效的策略之一。近年来,利用自然杀伤(NK)细胞进行癌症治疗取得了进展。NK细胞无需预先致敏即可直接杀伤肿瘤细胞,因此与T细胞的应用不同,在临床应用中显示出前景。然而,基于NK细胞的免疫治疗的研发仍处于起步阶段,增强NK细胞的治疗效果仍是一个亟待解决的关键问题。对NK细胞作用机制的不完全理解、肿瘤微环境中的免疫抵抗以及体内治疗药物递送相关的障碍,代表了三座需要翻越的大山。在此,我们首先描述NK细胞发育、活性和成熟以及NK细胞免疫突触形成的机制。其次,我们讨论基于NK细胞的免疫治疗策略,包括NK细胞过继转移治疗以及针对NK细胞的细胞因子、单克隆抗体和免疫检查点抑制剂治疗。最后,我们综述利用纳米技术克服免疫抵抗,包括增强嵌合抗原受体-NK、细胞因子和免疫抑制通路抑制剂的抗肿瘤效率,促进NK细胞归巢以及开发基于NK细胞的纳米衔接器。
Immunotherapy represents one of the most effective strategies for cancer treatment. Recently, progress has been made in using natural killer (NK) cells for cancer therapy. NK cells can directly kill tumor cells without pre-sensitization and thus show promise in clinical applications, distinct from the use of T cells.
Whereas, research and development on NK cell-based immunotherapy is still in its infancy, and enhancing the therapeutic effects of NK cells remains a key problem to be solved. An incompletely understanding of the mechanisms of action of NK cells, immune resistance in the tumor microenvironment, and obstacles associated with the delivery of therapeutic agents in vivo, represent three mountains that need to be scaled.
Here, we firstly describe the mechanisms underlying the development, activity, and maturation of NK cells, and the formation of NK cell immunological synapses. Secondly, we discuss strategies for NK cell-based immunotherapy strategies, including adoptive transfer of NK cell therapy and treatment with cytokines, monoclonal antibodies, and immune checkpoint inhibitors targeting NK cells.
Finally, we review the use of nanotechnology to overcome immune resistance, including enhancing the anti-tumor efficiency of chimeric antigen receptor-NK, cytokines and immunosuppressive-pathways inhibitors, promoting NK cell homing and developing NK cell-based nano-engagers.
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