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用于研究肿瘤微环境中自然杀伤细胞动态的模型。

models to study natural killer cell dynamics in the tumor microenvironment.

机构信息

Department of Applied Physics, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.

Center for Infectious Medicine, Department of Medicine Huddinge, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.

出版信息

Front Immunol. 2023 Jun 28;14:1135148. doi: 10.3389/fimmu.2023.1135148. eCollection 2023.

DOI:10.3389/fimmu.2023.1135148
PMID:37457703
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10338882/
Abstract

Immunotherapy is revolutionizing cancer therapy. The rapid development of new immunotherapeutic strategies to treat solid tumors is posing new challenges for preclinical research, demanding novel methods to test treatments. Such methods should meet specific requirements, such as enabling the evaluation of immune cell responses like cytotoxicity or cytokine release, and infiltration into the tumor microenvironment using cancer models representative of the original disease. They should allow high-throughput and high-content analysis, to evaluate the efficacy of treatments and understand immune-evasion processes to facilitate development of new therapeutic targets. Ideally, they should be suitable for personalized immunotherapy testing, providing information for patient stratification. Consequently, the application of 3-dimensional (3D) cell culture models, such as tumor spheroids and organoids, is rapidly expanding in the immunotherapeutic field, coupled with the development of novel imaging-based techniques and -omic analysis. In this paper, we review the recent advances in the development of 3D platforms applied to natural killer (NK) cell-based cancer immunotherapy studies, highlighting the benefits and limitations of the current methods, and discuss new concepts and future directions of the field.

摘要

免疫疗法正在彻底改变癌症治疗。新的免疫治疗策略在治疗实体瘤方面的快速发展,为临床前研究带来了新的挑战,需要新的方法来测试治疗方法。这些方法应该满足特定的要求,例如能够评估免疫细胞的反应,如细胞毒性或细胞因子释放,以及使用代表原始疾病的癌症模型评估浸润到肿瘤微环境中的情况。它们应该允许进行高通量和高内涵分析,以评估治疗的效果,并了解免疫逃逸过程,从而促进新治疗靶点的开发。理想情况下,它们应该适用于个性化免疫治疗测试,为患者分层提供信息。因此,3 维(3D)细胞培养模型,如肿瘤球体和类器官的应用,在免疫治疗领域迅速扩展,同时也伴随着新型成像技术和组学分析的发展。在本文中,我们综述了 3D 平台在自然杀伤(NK)细胞为基础的癌症免疫治疗研究中的最新进展,强调了当前方法的优势和局限性,并讨论了该领域的新概念和未来方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1787/10338882/5418e98a1999/fimmu-14-1135148-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1787/10338882/3554032a5fb4/fimmu-14-1135148-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1787/10338882/95b19abee80e/fimmu-14-1135148-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1787/10338882/0cf4d258ae9e/fimmu-14-1135148-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1787/10338882/2a7963efa89a/fimmu-14-1135148-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1787/10338882/5418e98a1999/fimmu-14-1135148-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1787/10338882/3554032a5fb4/fimmu-14-1135148-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1787/10338882/95b19abee80e/fimmu-14-1135148-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1787/10338882/0cf4d258ae9e/fimmu-14-1135148-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1787/10338882/2a7963efa89a/fimmu-14-1135148-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1787/10338882/5418e98a1999/fimmu-14-1135148-g005.jpg

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本文引用的文献

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Methods Cell Biol. 2023;178:195-208. doi: 10.1016/bs.mcb.2023.01.001. Epub 2023 Feb 16.
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Generation of NK cells with chimeric-switch receptors to overcome PD1-mediated inhibition in cancer immunotherapy.利用嵌合开关受体生成 NK 细胞以克服癌症免疫治疗中的 PD1 介导的抑制。
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A multi-organ-on-chip to recapitulate the infiltration and the cytotoxic activity of circulating NK cells in 3D matrix-based tumor model.
肝癌细胞对组蛋白去乙酰化酶抑制剂(HDACi)的敏感性通过人源miR-342-5p/丝切蛋白1(CFL1)进行调控。
Cancer Cell Int. 2024 Aug 16;24(1):291. doi: 10.1186/s12935-024-03450-x.
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Optimizing Ex Vivo CAR-T Cell-Mediated Cytotoxicity Assay through Multimodality Imaging.通过多模态成像优化离体CAR-T细胞介导的细胞毒性测定
Cancers (Basel). 2024 Jul 9;16(14):2497. doi: 10.3390/cancers16142497.
一种用于在基于三维基质的肿瘤模型中模拟循环自然杀伤细胞浸润和细胞毒性活性的多器官芯片。
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Miniaturized and multiplexed high-content screening of drug and immune sensitivity in a multichambered microwell chip.在多腔室微井芯片中对药物和免疫敏感性进行微型化和多重高内涵筛选。
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