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:Robo1 CAR-NK92 and radiotherapy exert synergistic efficacy in solid tumors.
Robo1 CAR-NK92 and radiotherapy exert synergistic efficacy in solid tumors.
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我们的结果表明,Robo1 CAR-NK92 疗法与放疗联合可能为实体瘤的治疗提供一种有前景的方法。
嵌合抗原受体自然杀伤(CAR-NK)细胞治疗实体瘤的疗效往往有限,主要原因是肿瘤微环境(TME)阻碍了CAR-NK细胞的识别和浸润。放疗已被证明可以改变TME,增强免疫细胞浸润,并改善免疫细胞对肿瘤细胞的识别。本研究旨在探讨在实体瘤模型中将放疗与CAR-NK细胞联合应用的效果。
开发了Robo1 CAR-NK92细胞系以特异性靶向Robo1。放疗后生成肿瘤细胞系,并在体外和体内评估了放疗后Robo1 CAR-NK92细胞在实体瘤模型中的细胞毒性和浸润能力。
放疗后,Robo1 CAR-NK92细胞对肿瘤细胞的细胞毒性显著增强,这可能是由于肿瘤细胞表面NKG2D配体上调所致。此外,发现放疗后的肿瘤细胞可促进Robo1 CAR-NK92细胞的迁移。在体内实验中,放疗与Robo1 CAR-NK92细胞联合应用在实体瘤小鼠模型中延长了生存期并改善了肿瘤控制。
The efficacy of chimeric antigen receptor natural killer (CAR-NK) cells in treating solid tumors is often limited, primarily due to the tumor microenvironment (TME), which hinders the recognition and infiltration of CAR-NK cells. Radiotherapy has been shown to modify the TME, enhance immune cell infiltration, and improve the recognition of tumor cells by immune cells. This study aimed to investigate the effects of combining radiotherapy with CAR-NK cells in a solid tumor model.
The Robo1 CAR-NK92 cell line was developed to specifically target Robo1. Tumor cell lines were generated following radiotherapy, and the cytotoxicity and infiltration of Robo1 CAR-NK92 cells in solid tumor models were evaluated both in vitro and in vivo post-radiotherapy.
The cytotoxicity of Robo1 CAR-NK92 cells against tumor cells was significantly enhanced following radiotherapy, likely due to the upregulation of NKG2D ligands on the surface of the tumor cells. Furthermore, tumor cells post-radiotherapy were found to promote the migration of Robo1 CAR-NK92 cells. In in vivo experiments, the combination of radiotherapy and Robo1 CAR-NK92 cells resulted in prolonged survival and improved tumor control in a solid tumor mouse model.
Our results indicate that the combination of Robo1 CAR-NK92 therapy and radiotherapy may present a promising approach for the treatment of solid tumors.
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