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:Granzyme B and melittin in cancer immunotherapy: molecular mechanisms and therapeutic perspectives in head and neck cancers.
Granzyme B and melittin in cancer immunotherapy: molecular mechanisms and therapeutic perspectives in head and neck cancers.
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颗粒酶B(GZMB)和蜂毒肽是强效的细胞毒性剂,在癌症免疫治疗中具有广阔的应用前景,尤其是在头颈部鳞状细胞癌(HNSC)中。GZMB由细胞毒性T淋巴细胞和自然杀伤(NK)细胞分泌,通过caspase激活和线粒体破坏诱导细胞凋亡。其在HNSC中的表达既与预后改善相关,又矛盾地通过调节性T细胞介导免疫抑制。蜂毒肽是一种来源于蜂毒的肽,通过破坏癌细胞膜、诱导氧化应激和激活凋亡通路发挥抗癌作用。尽管有效,但其非特异性细胞毒性构成了治疗挑战,目前正通过靶向递送系统(如纳米颗粒和脂质体)加以解决。本综述重点阐述GZMB和蜂毒肽在调节肿瘤细胞死亡和肿瘤微环境中各自不同但可能互补的作用。
我们还讨论了耐药机制,包括颗粒酶抑制剂(如PI-9)的表达、膜动力学改变以及G2/M细胞周期阻滞。将免疫介导的GZMB作用的特异性与蜂毒肽的广泛细胞毒性相结合,可能在未来治疗中提供协同获益。理解这些分子的机制为HNSC及其他实体瘤治疗中的新型免疫治疗策略奠定了基础。
Granzyme B (GZMB) and melittin are potent cytotoxic agents with promising applications in cancer immunotherapy, particularly in head and neck squamous cell carcinoma (HNSC). GZMB, secreted by cytotoxic T lymphocytes and natural killer (NK) cells, induces apoptosis through caspase activation and mitochondrial disruption. Its expression in HNSC correlates with both improved prognosis and, paradoxically, immune suppression via regulatory T cells.
Melittin, a peptide derived from bee venom, exerts anticancer effects by disrupting cancer cell membranes, inducing oxidative stress, and activating apoptotic pathways. While effective, its non-specific cytotoxicity poses a therapeutic challenge, which is being addressed through targeted delivery systems, such as nanoparticles and liposomes. This review highlights the distinct yet potentially complementary roles of GZMB and melittin in modulating tumor cell death and the tumor microenvironment.
We also discuss mechanisms of resistance, including expression of granzyme inhibitors (e. g. , PI-9), altered membrane dynamics, and G2/M cell cycle arrest. Combining the specificity of immune-mediated GZMB action with the broad cytotoxicity of melittin may offer synergistic benefits in future therapies. Understanding these molecules' mechanisms provides a foundation for novel immunotherapeutic strategies in the treatment of HNSC and other solid tumor.
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