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:Combining radiotherapy and NK cell-based therapies: The time has come.
Combining radiotherapy and NK cell-based therapies: The time has come.
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自然杀伤(NK)细胞是先天淋巴样细胞,通过免疫监视、多种细胞毒性机制以及合成调节免疫肿瘤微环境(TME)的细胞因子,在抗肿瘤反应中发挥重要作用。在靶向 T 细胞的免疫治疗取得显著进展之后,包括检查点抑制剂或表达自体嵌合抗原受体(CAR)的 T 细胞在临床实践中的成功,NK 细胞在开发新疗法方面获得了越来越多的关注。尽管 NK 细胞在白血病患者中显示出有前景的应答,但靶向 NK 细胞的疗法在实体瘤治疗中的效果目前仍然有限。
因此,放疗可能为改善靶向 NK 细胞的治疗提供有价值的解决方案。事实上,电离辐射是一种强大的免疫调节剂,既可以诱导促炎和抗肿瘤的 TME,也可以相反地导致效应免疫细胞的免疫抑制,从而有利于肿瘤生长和治疗逃逸,这取决于其递送方式和肿瘤模型。
然而,电离辐射对 NK 细胞的影响仅被部分了解。因此,我们综述放疗对 NK 细胞介导的抗肿瘤反应的影响,并提出通过将放疗与靶向 NK 细胞的疗法相结合来重新激活 NK 细胞的潜在策略。
Natural killer (NK) cells are innate lymphoid cells that play an essential role in the anti-tumor response through immunosurveillance, multiple mechanisms of cytotoxicity and the synthesis of cytokines modulating the immune tumor microenvironment (TME).
After the dramatic advances in immunotherapy targeting T cells including the success of checkpoint inhibitors or autologous chimeric antigen receptor (CAR) expressing T cells in clinical practice, NK cells have gained growing interest for the development of new therapies. Although NK cells have shown promising responses in leukemia patients, the effects of NK-targeted therapies are currently limited in the treatment of solid tumors.
Thus, radiotherapy could provide a valuable solution to improve treatments targeting NK cells. Indeed, ionizing radiations represent a powerful immuno-modulator that can either induce a pro-inflammatory and anti-tumor TME, or conversely lead to immunosuppression of effector immune cells in favor of tumor growth and therapeutic escape, depending on how it is delivered and tumor models.
However, the effects of ionizing radiation on NK cells are only partially understood.
Therefore, we review the effects of radiotherapy on the NK cell-mediated anti-tumor response, and propose potential strategies to reinvigorate NK cells by combining radiotherapy with NK cell-targeted therapies.
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