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:A three-dimensional immune-oncology model for studying in vitro primary human NK cell cytotoxic activity.
A three-dimensional immune-oncology model for studying in vitro primary human NK cell cytotoxic activity.
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免疫疗法已成为治疗多种癌症的一种有前景的治疗方法。免疫细胞的过继性细胞转移,如自然杀伤(NK)细胞,提供了强大的抗肿瘤治疗潜力。在过去几十年中,二维(2D)肿瘤模型已被用于研究免疫细胞杀伤的有效性。然而,2D肿瘤模型结构复杂性较低,无法再现肿瘤微环境的生理条件。因此,使用这些模型评估免疫细胞对肿瘤细胞的有效性无法完全转化为临床研究。为了更深入地了解免疫细胞与肿瘤的相互作用,已开发出更接近生理条件的体内样三维(3D)肿瘤模型。这些3D肿瘤模型能够模拟动态细胞活动,使其更接近体内肿瘤特征。在此,我们描述了一种简单有效的方案,用于研究原代人NK细胞对3D肿瘤球体的细胞毒性活性。我们的方案包括人NK细胞的分离和扩增、肿瘤球体的标记和形成、NK细胞与肿瘤球体的共培养,以及使用共聚焦显微镜评估细胞毒性活性。该方案也适用于其他类型的肿瘤和免疫细胞。
Immunotherapy has emerged as a promising therapeutic approach for treating several forms of cancer. Adoptive cell transfer of immune cells, such as natural killer (NK) cells, provides a powerful therapeutic potential against tumor cells. In the past decades, two-dimensional (2D) tumor models have been used to investigate the effectiveness of immune cell killing.
However, the 2D tumor models exhibit less structural complexity and cannot recapitulate the physiological condition of the tumor microenvironment.
Thus, the effectiveness of immune cells against tumor cells using these models cannot fully be translated to clinical studies. In order to gain a deeper insight into immune cell-tumor interaction, more physiologically relevant in vivo-like three-dimensional (3D) tumor models have been developed. These 3D tumor models can mimic the dynamic cellular activities, making them a much closer representation of the in vivo tumor profiles.
Here, we describe a simple and effective protocol to study the cytotoxic activity of primary human NK cells toward the 3D tumor spheroids.
Our protocol includes isolation and expansion of human NK cells, labeling and formation of tumor spheroids, co-culture of NK cells and tumor spheroids, and evaluation of cytotoxic activity using a confocal microscope. This protocol is also applicable to other types of tumors and immune cells.
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