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-based cytokine delivery strategies in gastrointestinal cancers.
Nanotechnology-based cytokine delivery strategies in gastrointestinal cancers.
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胃肠道(GI)肿瘤,包括结直肠、胃和食管恶性肿瘤,仍然是全球主要的健康负担,尽管诊断和常规治疗取得了进展,其发病率和死亡率仍然很高。基于细胞因子的免疫治疗已成为调节肿瘤微环境和增强抗肿瘤免疫的有前景的策略。
然而,其临床转化受到快速降解、全身毒性和肿瘤特异性递送不佳的限制。纳米技术驱动的递送平台,包括脂质体、聚合物纳米颗粒、外泌体、水凝胶和智能纳米载体,通过实现靶向、可控和持续的细胞因子释放,提供了创新的解决方案。这些系统增强免疫细胞活化,重编程肿瘤微环境,并与免疫检查点抑制剂、化疗、放疗和过继性T细胞治疗产生协同作用。近期的临床前研究表明,工程化纳米颗粒可以放大CD8⁺ T细胞和NK细胞反应,减少脱靶效应,并改善GI肿瘤的治疗效果。先进的设计,如逐层纳米颗粒、受体靶向脂质体和多功能纳米载体,允许局部细胞因子递送、改善肿瘤特异性蓄积并降低全身毒性。尽管取得了这些进展,挑战仍然存在,包括生物屏障、细胞因子不稳定性、免疫原性和制造复杂性。未来的方向在于精准纳米医学和合成生物学方法,将工程化细胞因子与多功能纳米载体整合,以实现安全、有效和患者特异性的免疫治疗。
总体而言,纳米技术驱动的细胞因子递送代表了一种变革性方法,具有克服当前局限性并增强胃肠道恶性肿瘤免疫治疗疗效的潜力。
Gastrointestinal (GI) cancers, including colorectal, gastric, and esophageal malignancies, remain a major global health burden, with high incidence and mortality despite advances in diagnostics and conventional therapies. Cytokine-based immunotherapies have emerged as promising strategies to modulate the tumor microenvironment and enhance antitumor immunity.
However, their clinical translation is limited by rapid degradation, systemic toxicity, and poor tumor-specific delivery. Nanotechnology-driven delivery platforms, including liposomes, polymeric nanoparticles, exosomes, hydrogels, and smart nanocarriers, offer innovative solutions by enabling targeted, controlled, and sustained cytokine release. These systems enhance immune cell activation, reprogram the tumor microenvironment, and synergize with immune checkpoint inhibitors, chemotherapy, radiotherapy, and adoptive T cell therapies. Recent preclinical studies demonstrate that engineered nanoparticles can amplify CD8⁺ T and NK cell responses, reduce off-target effects, and improve therapeutic outcomes in GI cancers.
Advanced designs,such as layer-by-layer nanoparticles, receptor-targeted liposomes, and multifunctional nanocarriers allow localized cytokine delivery, improved, tumor-specific accumulation, and reduced systemic toxicity. Despite these advances, challenges remain, including biological barriers, cytokine instability, immunogenicity, and manufacturing complexity.
Future directions lie in precision nanomedicine and synthetic biology approaches integrating engineered cytokines with multifunctional nanocarriers to achieve safe, effective, and patient-specific immunotherapy. Collectively, nanotechnology-driven cytokine delivery represents a transformative approach with the potential to overcome current limitations and enhance the efficacy of immunotherapy for gastrointestinal malignancies.
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