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:The Biological Role and Therapeutic Potential of NK Cells in Hematological and Solid Tumors.
The Biological Role and Therapeutic Potential of NK Cells in Hematological and Solid Tumors.
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NK 细胞因其强大的抗肿瘤活性而成为癌症免疫治疗的一个有吸引力的靶点。与 T 细胞相比,使用 NK 细胞作为细胞毒性效应细胞的主要优势在于移植物抗宿主病的风险降低。目前,几种基于 NK 细胞的治疗变体正在进行临床试验,并在血液系统肿瘤中显示出相当大的疗效。在这类癌症中,免疫细胞本身往往发生恶性转化,这决定了疾病特征。相比之下,目前使用 NK 细胞作为实体瘤治疗药物的前景则远不那么乐观。大多数研究处于临床前研究阶段,但很少有进展到临床试验。NK 细胞在肿瘤环境中迁移效率低和功能活性低目前被认为是 NK 细胞抗肿瘤治疗的主要障碍。各种治疗组合、基因工程方法、获取 NK 细胞的替代来源以及其他技术都旨在开发有前景的 NK 细胞抗癌疗法,无论肿瘤发生机制如何。在这篇综述中,我们比较了 NK 细胞在血液系统肿瘤和实体瘤发病机制中的作用,并讨论了基于 NK 细胞的疗法用于血液系统肿瘤和实体瘤的当前前景。
NK cells are an attractive target for cancer immunotherapy due to their potent antitumor activity. The main advantage of using NK cells as cytotoxic effectors over T cells is a reduced risk of graft versus host disease. At present, several variants of NK-cell-based therapies are undergoing clinical trials and show considerable effectiveness for hematological tumors. In these types of cancers, the immune cells themselves often undergo malignant transformation, which determines the features of the disease. In contrast, the current use of NK cells as therapeutic agents for the treatment of solid tumors is much less promising.
Most studies are at the stage of preclinical investigation, but few progress to clinical trials. Low efficiency of NK cell migration and functional activity in the tumor environment are currently considered the major barriers to NK cell anti-tumor therapies.
Various therapeutic combinations, genetic engineering methods, alternative sources for obtaining NK cells, and other techniques are aiming at the development of promising NK cell anticancer therapies, regardless of tumorigenesis. In this review, we compare the role of NK cells in the pathogenesis of hematological and solid tumors and discuss current prospects of NK-cell-based therapy for hematological and solid tumors.
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