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 cells and engagers: Powerful weapons against cancer.
Natural killer cells and engagers: Powerful weapons against cancer.
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自然杀伤(NK)细胞是先天免疫效应细胞,其功能依赖于受体结合细胞因子、识别自身分子或检测病毒感染细胞或肿瘤细胞表达的危险信号。强大的细胞毒性潜力使NK细胞成为癌症免疫治疗的有前景的候选者。为增强其活性,策略包括给予细胞因子、阻断免疫检查点以及设计基于抗体的NK细胞衔接器(NKCEs)。NKCEs代表了一种癌症治疗的前沿方法:它们增强NK细胞与靶细胞的相互作用并优化肿瘤杀伤,可能克服免疫抑制性肿瘤微环境。NK细胞属于先天淋巴细胞(ILCs),并被分为不同亚群,也包括具有记忆样表型的细胞:这种复杂性需要在癌症免疫治疗的背景下进行探索,尤其是在设计NKCEs时。可以采用两种策略来增强癌症患者的NK细胞活性:激活患者自身的NK细胞与过继转移体外活化的NK细胞。此外,NKCEs激活T细胞的能力可能在免疫治疗中产生显著的协同效应。
Natural killer (NK) cells are innate immune effectors whose functions rely on receptors binding cytokines, recognizing self-molecules, or detecting danger signals expressed by virus-infected or tumor cells. The potent cytotoxic potential makes NK cells promising candidates for cancer immunotherapy. To enhance their activity strategies include cytokine administration, blocking of immune checkpoints, and designing of antibody-based NK cell engagers (NKCEs).
NKCEs represent a cutting-edge approach to cancer therapy: they strengthen the NK-to-target cell interactions and optimize tumor killing, possibly overcoming the immunosuppressive tumor microenvironment.
NK cells belong to the innate lymphoid cells (ILCs) and are categorized into different subsets also including cells with a memory-like phenotype: this complexity needs to be explored in the context of cancer immunotherapy, particularly when designing NKCEs. Two strategies to enhance NK cell activity in cancer patients can be adopted: activating patients' own NK cells versus the adoptive transfer of ex vivo activated NK cells.
Furthermore, the capability of NKCEs to activate T cells could have a significant synergistic effect in immunotherapy.
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