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:Breaking boundaries: Current progress of anticancer NK cell-based drug development.
Breaking boundaries: Current progress of anticancer NK cell-based drug development.
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自然杀伤(NK)细胞疗法正在成为一种癌症治疗方法。NK细胞是先天细胞毒性淋巴细胞,作为一线应答者,无需先前接触即可杀死靶细胞。NK细胞通过一组种系编码的受体库识别癌细胞、病毒感染细胞和其他类型的应激细胞。NK细胞对于异体应用是安全的。因此,它们是理想的现货型细胞,克服了自体细胞疗法因患者个体化特性导致的低效率问题。与T细胞不同,NK细胞无法形成强烈的免疫记忆;因此,它们在体内持久性较短。然而,与T细胞不同的是,NK细胞拥有针对多种恶性细胞的先天免疫受体库。此外,它们可以利用抗体引导进行靶标识别。通过合适的工程改造,NK细胞可以作为不受HLA和癌症类型限制的通用抗癌药物,这将惠及大量罕见癌症类型患者以及没有便捷药物靶点用于精准和个性化医疗的患者。在此,我们总结并讨论了当前抗癌NK细胞疗法的设计。
Natural killer (NK) cell therapy is emerging as a cancer treatment. NK cells are innate cytotoxic lymphocytes that act as first-line responders to kill target cells without prior encounters. NK cells recognize cancer cells, virus-infected cells, and other types of stressed cell through a reservoir of germline-encoded receptors. NK cells are safe for allogeneic applications.
Therefore, they are the ideal off-the-shelf cell, which overcome the low efficiency issue caused by the patient-by-patient nature of autologous cell therapy. Unlike T cells, NK cells cannot form a strong immune memory; therefore, they suffer from short in vivo persistence.
However, different from T cells, NK cells have a reservoir of innate immune receptors targeting a variety of malignant cells.
In addition, they can utilize antibody guidance in target recognition. With suitable engineering, NK cells can function as universal anticancer drugs that are not restricted to HLA and cancer types, which will benefit the large cohort of patients with rare cancer types and patients with no convenient drug targets for precision and personalized medicine.
Here, we summarize and discuss the designs of current anticancer NK cell therapies.
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