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:Stem cells-derived natural killer cells for cancer immunotherapy: current protocols, feasibility, and benefits of ex vivo generated natural killer cells in treatment of advanced solid tumors.
Stem cells-derived natural killer cells for cancer immunotherapy: current protocols, feasibility, and benefits of ex vivo generated natural killer cells in treatment of advanced solid tumors.
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目前,以自然杀伤(NK)细胞为基础的免疫疗法为晚期实体瘤患者提供了切实可行的治疗策略。此方法通常采用患者自体 NK 细胞,体外扩增并过夜活化后回输。然而,NK 细胞癌症免疫疗法仍面临一些基本和技术局限。此外,复杂的肿瘤微环境会抑制植入 NK 细胞在肿瘤内的极化和细胞毒性,可能导致疗效不理想。目前,干细胞(SC)技术为制备更有效且通用的 NK 细胞来源提供了有力机会。迄今已有多种策略,可通过依赖或不依赖饲养层的方法,将多能或成体干细胞分化为成熟 NK 细胞。这些干细胞来源 NK 细胞的主要特点包括细胞因子产生增加、肿瘤内极化能力增强及抗肿瘤特性更强。本综述聚焦晚期实体瘤患者常规 NK 细胞免疫疗法面临的主要障碍,并全面汇总体外生成干细胞来源 NK 细胞的方案。
Nowadays, natural killer (NK) cell-based immunotherapy provides a practical therapeutic strategy for patients with advanced solid tumors (STs). This approach is adaptively conducted by the autologous and identical NK cells after in vitro expansion and overnight activation.
However, the NK cell-based cancer immunotherapy has been faced with some fundamental and technical limitations.
Moreover, the desirable outcomes of the NK cell therapy may not be achieved due to the complex tumor microenvironment by inhibition of intra-tumoral polarization and cytotoxicity of implanted NK cells. Currently, stem cells (SCs) technology provides a powerful opportunity to generate more effective and universal sources of the NK cells. Till now, several strategies have been developed to differentiate types of the pluripotent and adult SCs into the mature NK cells, with both feeder layer-dependent and/or feeder laye-free strategies.
Higher cytokine production and intra-tumoral polarization capabilities as well as stronger anti-tumor properties are the main features of these SCs-derived NK cells. The present review article focuses on the principal barriers through the conventional NK cell immunotherapies for patients with advanced STs. It also provides a comprehensive resource of protocols regarding the generation of SCs-derived NK cells in an ex vivo condition.
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