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:Remodeling the Tumor Microenvironment: Mechanistic Insights and Translational Frontiers of TCM-Derived Bioactive Monomers.
Remodeling the Tumor Microenvironment: Mechanistic Insights and Translational Frontiers of TCM-Derived Bioactive Monomers.
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近期研究表明,肿瘤发展和治疗耐药与肿瘤微环境(TME)密切相关,TME是一个由血管网络、免疫细胞和基质细胞、细胞外基质成分、细胞因子及细胞外囊泡组成的动态生态系统。本综述总结了目前关于中药来源的生物活性单体及纯化活性组分,包括多糖、皂苷、生物碱、萜类、黄酮类和多酚类化合物,如何调控TME相关过程的机制证据。据报道,这些化合物可调节巨噬细胞极化、T细胞和自然杀伤(NK)细胞监视、树突状细胞成熟、髓源性抑制细胞(MDSC)和中性粒细胞活性、癌症相关成纤维细胞(CAF)活化、血管生成信号、细胞因子网络、外泌体介导的通讯以及细胞外基质重塑。
然而,大多数现有证据仍来源于细胞模型和动物实验,临床验证有限。因此,中药来源的生物活性单体目前应被视为机制探针、先导结构或候选辅助药物,而非已确立的TME靶向疗法。未来研究应优先关注化合物标准化、剂量-反应关系、药代动力学和毒理学表征、可重复的模型系统、经验证的TME生物标志物以及对照临床试验。
Recent studies have shown that tumor development and therapeutic resistance are closely linked to the tumor microenvironment (TME), a dynamic ecosystem composed of vascular networks, immune and stromal cells, extracellular matrix components, cytokines, and extracellular vesicles. This review summarizes current mechanistic evidence on how bioactive monomers and purified active fractions derived from traditional Chinese medicine (TCM), including polysaccharides, saponins, alkaloids, terpenoids, flavonoids, and polyphenols, regulate TME-associated processes.
These compounds have been reported to modulate macrophage polarization, T-cell and natural killer (NK)-cell surveillance, dendritic-cell maturation, myeloid-derived suppressor cell (MDSC) and neutrophil activities, cancer-associated fibroblast (CAF) activation, angiogenic signaling, cytokine networks, exosome-mediated communication, and extracellular matrix remodeling.
However, most available evidence remains derived from cell models and animal experiments, and clinical validation is limited.
Therefore, TCM-derived bioactive monomers should currently be interpreted as mechanistic probes, lead structures, or candidate adjunctive agents rather than established TME-directed therapies. Future research should prioritize compound standardization, dose-response relationships, pharmacokinetic and toxicological characterization, reproducible model systems, validated TME biomarkers, and controlled clinical trials.
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