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:Cytokines in Focus: IL-2 and IL-15 in NK Adoptive Cell Cancer Immunotherapy.
Cytokines in Focus: IL-2 and IL-15 in NK Adoptive Cell Cancer Immunotherapy.
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NK细胞过继细胞治疗(ACT)已成为癌症免疫治疗的一种有前景策略,具有可扩展性、可及性、疗效和安全性方面的优势。采用饲养细胞和细胞因子组合的体外活化与扩增方案,已可生产具有高功能且数量达到临床相关水平的NK细胞。NK细胞工程技术的进步,包括CRISPR介导的基因编辑和嵌合抗原受体技术,进一步增强了其细胞毒性、持久性和肿瘤靶向能力。过继转移后给予细胞因子支持,尤其是IL-2和IL-15,对于促进NK细胞存活、增殖和抗肿瘤活性仍至关重要,尽管调节性T细胞扩增及细胞因子相关毒性等挑战依然存在。本综述探讨IL-2和IL-15在NK细胞ACT中的不断演变的作用,评估其潜力和局限,并介绍优化这些细胞因子以实现有效癌症免疫治疗的策略。
NK cell adoptive cell therapy (ACT) has emerged as a promising strategy for cancer immunotherapy, offering advantages in scalability, accessibility, efficacy, and safety. Ex vivo activation and expansion protocols, incorporating feeder cells and cytokine cocktails, have enabled the production of highly functional NK cells in clinically relevant quantities. Advances in NK cell engineering, including CRISPR-mediated gene editing and chimeric Ag receptor technologies, have further enhanced cytotoxicity, persistence, and tumor targeting.
Cytokine support post-adoptive transfer, particularly with IL-2 and IL-15, remains critical for promoting NK cell survival, proliferation, and anti-tumor activity despite persistent challenges such as regulatory T cell expansion and cytokine-related toxicities. This review explores the evolving roles of IL-2 and IL-15 in NK cell-based ACT, evaluating their potential and limitations, and highlights strategies to optimize these cytokines for effective cancer immunotherapy.
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