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结直肠癌中翻译后修饰的免疫调节作用:机制与治疗意义

英文原题:Immunoregulatory roles of post-translational modifications in colorectal cancer: mechanisms and therapeutic implications.

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Immunoregulatory roles of post-translational modifications in colorectal cancer: mechanisms and therapeutic implications.

PubMed 2025/12/08(内容时间) Cell Mol Life Sci Q1 · IF 6.5(JCR 2025)

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中文摘要

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。

展开英文摘要原文

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.

论文信息

作者
Liang X、Yao J、Jiao W、Li X、Yang B、Fan H
第一作者单位
Departments of Hematology, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.China
通讯作者单位
Departments of Hematology, The First Hospital of Jilin University, Changchun, Jilin, 130021, China. fanhq@jlu.edu.cn.China
文献类型
综述
期刊
Cellular and molecular life sciences : CMLS2025 Dec 8
原文标识
PubMed 41359051 · DOI 10.1007/s00018-025-05992-3