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:Nanotechnology and natural killer cell immunotherapy: synergistic approaches for precise immune system adjustment and targeted cancer treatment in gastrointestinal tumors.
Nanotechnology and natural killer cell immunotherapy: synergistic approaches for precise immune system adjustment and targeted cancer treatment in gastrointestinal tumors.
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胃肠道(GI)肿瘤是全球癌症相关疾病和死亡的主要贡献者,其特征是生长迅速、发现较晚以及对标准治疗耐药。NK 细胞是先天免疫系统的关键细胞毒性成分,因其能够靶向肿瘤细胞而无需抗原呈递,在免疫治疗中显示出前景。
然而,其针对胃肠道肿瘤的有效性受到肿瘤穿透不足、体内存活时间短以及免疫抑制性肿瘤微环境(TME)抑制等问题的限制。与此同时,纳米技术通过提供精确药物递送、免疫系统调节和改善生物利用度的方法,改变了癌症治疗。将 NK 细胞与专门设计的纳米颗粒(NPs)相结合,创建了一个强大的系统,具有增强的协同抗肿瘤效果,改善了肿瘤靶向、NK 细胞激活及其持久性,同时还允许在空间和时间上控制肿瘤免疫微环境。这篇全面的综述探讨了 NK 细胞免疫生物学与纳米材料设计之间复杂的相互作用,特别是在胃肠道肿瘤的背景下。重点关注领域包括纳米颗粒辅助的 NK 细胞工程、细胞因子递送、仿生伪装、TME 重编程以及特异性靶向肿瘤。
我们批判性地评估了支持这些联合疗法有效性的临床前和新兴临床证据,分析了相关的安全性和转化挑战,并提出了涉及基因编辑、创新刺激响应系统和 AI 辅助治疗个性化的前瞻性方法。
总之,本综述将 NK-NP 联合方法呈现为推进胃肠道癌症个性化、免疫引导治疗的一个有前景的新前沿。
Gastrointestina (GI) tumors are a major contributor to global cancer-related illness and death, marked by their rapid growth, late detection, and resistance to standard treatments. NK cells, key cytotoxic components of the innate immune system, show promise in immunotherapy due to their ability to target tumor cells without requiring antigen presentation. Nonetheless, their effectiveness against gastrointestinal tumors is constrained by issues such as insufficient tumor penetration, brief survival in the body, and suppression by the immunosuppressive tumor microenvironment (TME). Meanwhile, nanotechnology has transformed cancer treatment by offering methods for precise drug delivery, immune system modulation, and improved bioavailability.
Combining NK cells with specially designed nanoparticles (NPs) has created a powerful system with amplified cooperative anti-tumor effects, improving the targeting of tumors, activation of NK cells, and their endurance, while also allowing for control over the tumor immune microenvironment in both space and time.
This thorough review investigates the complex interaction between the immunobiology of NK cells and the design of nanomaterials, specifically in the context of gastrointestinal tumors. Key areas of focus include nanoparticle-assisted engineering of NK cells, cytokine delivery, biomimetic disguise, reprogramming of the TME, and targeting of tumors specifically.
We critically assess preclinical and emerging clinical evidence that supports the effectiveness of these combined therapies, analyze related safety and translational challenges, and suggest forward-looking approaches involving gene editing, innovative stimulus-responsive systems, and AI-assisted therapeutic personalization.
In conclusion, this review presents the combined NK-NP approach as a promising new frontier in the advancement of personalized, immune-guided treatments for gastrointestinal cancers.
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