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 War Is on: The Immune System against Glioblastoma-How Can NK Cells Drive This Battle?
The War Is on: The Immune System against Glioblastoma-How Can NK Cells Drive This Battle?
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自然杀伤(NK)细胞是先天淋巴细胞,在免疫监视中发挥重要作用,与其他免疫细胞一起参与对各类恶性肿瘤的应答及转移的预防。自20世纪70年代被发现以来,人们对其无需预先致敏即可杀伤肿瘤细胞的能力进行了深入研究,NK细胞能执行快速而强大的细胞毒活性,同时也具有辅助功能。据此,NK细胞正以多种方式被用于治疗癌症。基于NK细胞的治疗手段广泛,包括过继转移体外扩增和活化的细胞、通过基因工程使其携带嵌合抗原受体(CAR-NK)、体内刺激NK细胞(通过细胞因子治疗、检查点阻断治疗等),以及肿瘤特异性抗体引导的NK细胞等。本文中,我们综述了NK细胞生物学的关键方面及其对抗肿瘤免疫应答的贡献,并对使用NK细胞的多种抗肿瘤策略提供了广阔视角。最后,我们还讨论了那些有潜力控制胶质母细胞瘤的方法——该疾病目前会导致不可避免的死亡,通常在诊断后短时间内发生。
Natural killer (NK) cells are innate lymphocytes that play an important role in immunosurveillance, acting alongside other immune cells in the response against various types of malignant tumors and the prevention of metastasis. Since their discovery in the 1970s, they have been thoroughly studied for their capacity to kill neoplastic cells without the need for previous sensitization, executing rapid and robust cytotoxic activity, but also helper functions. In agreement with this, NK cells are being exploited in many ways to treat cancer.
The broad arsenal of NK-based therapies includes adoptive transfer of in vitro expanded and activated cells, genetically engineered cells to contain chimeric antigen receptors (CAR-NKs), in vivo stimulation of NK cells (by cytokine therapy, checkpoint blockade therapies, etc.) , and tumor-specific antibody-guided NK cells, among others. In this article, we review pivotal aspects of NK cells' biology and their contribution to immune responses against tumors, as well as providing a wide perspective on the many antineoplastic strategies using NK cells.
Finally, we also discuss those approaches that have the potential to control glioblastoma-a disease that, currently, causes inevitable death, usually in a short time after diagnosis.
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