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:Cytokine-induced memory-like natural killer cells for cancer immunotherapy.
Cytokine-induced memory-like natural killer cells for cancer immunotherapy.
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NK 细胞是固有免疫系统的重要组成部分,无需预先抗原致敏即可介导对病毒感染细胞和恶性细胞的强效应答。NK 细胞一直被认为寿命短且无抗原特异性;然而,近期数据支持 NK 细胞记忆的存在,包括在半抗原特异性接触性超敏模型和某些病毒感染中。通过 IL-12、IL-15 和 IL-18 的细胞因子组合短期激活小鼠和人 NK 细胞,也可产生记忆样特征,赋予其更长的寿命和增强的抗癌功能。临床前研究和极早期临床试验表明,这些细胞因子诱导的记忆样(CIML)NK 细胞具有安全性和非常有前景的临床活性,使其成为开发新型过继细胞免疫治疗策略的有吸引力的细胞类型。此外,正在努力为其装备新型基因构建体,以增强肿瘤靶向性和功能。
Natural killer cells are an important part of the innate immune system mediating robust responses to virus-infected and malignant cells without needing prior antigen priming. NK cells have always been thought to be short-lived and with no antigen specificity; however, recent data support the presence of NK cell memory including in the hapten-specific contact hypersensitivity model and in certain viral infections.
The memory-like features can also be generated by short-term activation of both murine and human NK cells with cytokine combination of IL-12, IL-15 and IL-18, imparting increased longevity and enhanced anticancer functionality. Preclinical studies and very early clinical trials demonstrate safety and very promising clinical activity of these cytokine-induced memory-like (CIML) NK cells, making them an attractive cell type for developing novel adoptive cellular immunotherapy strategies.
Furthermore, efforts are on to arm them with novel gene constructs for enhanced tumor targeting and function.
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