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:Combined use of NK cells and radiotherapy in the treatment of solid tumors.
Combined use of NK cells and radiotherapy in the treatment of solid tumors.
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自然杀伤(NK)细胞是先天淋巴细胞,具有强大的肿瘤监视和清除活性。NK细胞在综合性抗肿瘤策略(尤其是免疫治疗)中的作用正受到越来越多的关注。
值得注意的是,治疗效果在很大程度上取决于两个参数:NK细胞在肿瘤微环境(TME)中的浸润和细胞毒性,而这两者均受到若干障碍(如趋化因子、缺氧)的损害。需要克服这些障碍的策略。放疗是用于治疗实体瘤的常规手段。近期研究表明,放疗不仅直接损伤肿瘤细胞,还通过原位效应或远隔效应改变肿瘤或免疫细胞的分子表达,从而增强免疫细胞对肿瘤的识别。
因此,放疗可能重建一个有利于NK细胞的TME,从而提供一种经济有效的方法来改善NK细胞向实体瘤的浸润,并提升免疫活性。此外,肿瘤的放射抵抗常常阻碍对放疗的应答。
值得注意的是,NK细胞强大的细胞毒性活性不仅直接杀伤肿瘤细胞,还通过激活若干放射增敏通路来增加肿瘤对放射的应答。在此,我们综述NK细胞与放疗相互促进其杀伤实体恶性肿瘤功能的机制。我们还讨论了在联合抗癌治疗中利用这些特征的潜在策略。
Natural killer (NK) cells are innate lymphocytes possessing potent tumor surveillance and elimination activity. Increasing attention is being focused on the role of NK cells in integral antitumor strategies (especially immunotherapy). Of note, therapeutic efficacy is considerable dependent on two parameters: the infiltration and cytotoxicity of NK cells in tumor microenvironment (TME), both of which are impaired by several obstacles (e.
g. , chemokines, hypoxia). Strategies to overcome such barriers are needed. Radiotherapy is a conventional modality employed to cure solid tumors. Recent studies suggest that radiotherapy not only damages tumor cells directly, but also enhances tumor recognition by immune cells through altering molecular expression of tumor or immune cells via the in situ or abscopal effect.
Thus, radiotherapy may rebuild a NK cells-favored TME, and thus provide a cost-effective approach to improve the infiltration of NK cells into solid tumors, as well as elevate immune-activity.
Moreover, the radioresistance of tumor always hampers the response to radiotherapy. Noteworthy, the puissant cytotoxic activity of NK cells not only kills tumor cells directly, but also increases the response of tumors to radiation via activating several radiosensitization pathways.
Herein, we review the mechanisms by which NK cells and radiotherapy mutually promote their killing function against solid malignancies.
We also discuss potential strategies harnessing such features in combined anticancer care.
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