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NK 细胞与放疗联合用于实体瘤治疗。

Combined use of NK cells and radiotherapy in the treatment of solid tumors.

机构信息

Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Institution of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

Front Immunol. 2024 Jan 9;14:1306534. doi: 10.3389/fimmu.2023.1306534. eCollection 2023.

Abstract

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 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.

摘要

自然杀伤 (NK) 细胞是具有强大肿瘤监测和消除活性的先天淋巴细胞。人们越来越关注 NK 细胞在整体抗肿瘤策略(特别是免疫疗法)中的作用。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,这两者都受到多种障碍的损害(例如趋化因子、缺氧)。需要克服这些障碍的策略。放射疗法是一种用于治疗实体瘤的常规方法。最近的研究表明,放射疗法不仅直接损伤肿瘤细胞,还通过改变肿瘤或免疫细胞的分子表达,通过远隔效应或直接效应增强免疫细胞对肿瘤的识别。因此,放射疗法可能重建 NK 细胞有利的 TME,从而提供一种具有成本效益的方法来改善 NK 细胞浸润实体瘤,并提高免疫活性。此外,肿瘤的放射抗性总是阻碍对放射疗法的反应。值得注意的是,NK 细胞强大的细胞毒性不仅直接杀死肿瘤细胞,还通过激活几种放射增敏途径增加肿瘤对辐射的反应。本文综述了 NK 细胞和放射疗法相互促进对实体恶性肿瘤杀伤功能的机制。我们还讨论了利用这些特征在联合抗癌治疗中的潜在策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/168b/10803658/db72218cea47/fimmu-14-1306534-g001.jpg

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