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:Immunoregulatory roles of post-translational modifications in colorectal cancer: mechanisms and therapeutic implications.
Immunoregulatory roles of post-translational modifications in colorectal cancer: mechanisms and therapeutic implications.
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结直肠癌(CRC)仍然是全球癌症发病和死亡的主要原因,肿瘤免疫逃逸是有效免疫治疗面临的主要挑战。翻译后修饰(PTM),包括磷酸化、泛素化、乙酰化、甲基化和糖基化,是蛋白质功能和稳定性的关键调控因素,深刻影响肿瘤免疫原性和肿瘤免疫微环境。本综述全面探讨了PTM如何调控CRC中的关键免疫过程,如抗原呈递、免疫细胞浸润和免疫检查点调控。我们讨论了PTM介导的机制,这些机制塑造了肿瘤微环境中的T细胞耗竭、巨噬细胞极化和免疫抑制性细胞因子网络。此外,我们重点阐述了PTM对免疫检查点阻断和过继细胞治疗的治疗反应和耐药性的影响。重点放在新兴的PTM靶向策略上,以增强抗肿瘤免疫并克服免疫治疗耐药。最后,我们探讨了多组学技术和蛋白质组学分析的进展,这些进展有望加速PTM生物标志物和新治疗靶点的发现。通过将机制见解与转化视角相结合,本综述旨在为利用PTM优化结直肠癌免疫治疗方法提供基础。
Colorectal cancer (CRC) remains a leading cause of cancer morbidity and mortality worldwide, with tumor immune evasion posing a major challenge to effective immunotherapy. Post-translational modifications (PTMs), including phosphorylation, ubiquitination, acetylation, methylation, and glycosylation, are critical regulators of protein function and stability, profoundly influencing tumor immunogenicity and the tumor immune microenvironment.
This review comprehensively examines how PTMs modulate key immune processes in CRC, such as antigen presentation, immune cell infiltration, and immune checkpoint regulation.
We discuss PTM-mediated mechanisms that shape T cell exhaustion, macrophage polarization, and immunosuppressive cytokine networks within the tumor microenvironment.
Moreover, we highlight the impact of PTMs on therapeutic response and resistance to immune checkpoint blockade and adoptive cell therapies. Emphasis is placed on emerging PTM-targeted strategies to enhance antitumor immunity and overcome immunotherapy resistance.
Finally, we explore advances in multi-omics technologies and proteomic profiling that promise to accelerate the identification of PTM biomarkers and novel therapeutic targets. By integrating mechanistic insights with translational perspectives, this review aims to provide a foundation for leveraging PTMs to optimize immunotherapeutic approaches in colorectal cancer.
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