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:The significance of trained immunity in cancer.
The significance of trained immunity in cancer.
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训练免疫(TI)代表了一种独特的天然免疫激活状态,其主要特征为免疫细胞中持续的表观遗传修饰。该现象最初在病原体感染和疫苗接种过程中被观察到,表现为天然免疫效应细胞——如单核吞噬细胞系统和NK 细胞——在再次刺激时防御反应增强。癌症是一种机制复杂的疾病,以细胞因基因突变或表观遗传失调而丧失正常生长调控为特征,导致异常增殖和播散。癌症有数百种亚型,几乎可发生于人体的任何组织或器官。癌症相关死亡的主要原因转移,是指癌细胞从原发部位扩散至远处器官,约占全球癌症死亡的90%。TI的诱导涉及多种免疫组分,包括髓系细胞、NK 细胞、模式识别受体以及多种细胞因子。
值得注意的是,二次刺激中观察到的增强反应对特定病原体并不具有特异性。与传统治疗方法相比,TI表现出更优越的全身性免疫激活。简单的药理学刺激如β-葡聚糖或卡介苗(BCG)不仅能触发天然免疫应答,还能为适应性免疫带来益处,从而实现更快速的免疫激活和更强的疗效。TI增强了免疫细胞识别和清除癌细胞的能力,在对抗转移中发挥关键作用。在本综述中,我们总结了该领域的现有知识,重点关注TI诱导的机制及其在对抗癌症中的意义。
Trained immunity (TI) represented a unique state of innate immune activation, characterized primarily by persistent epigenetic modifications in immune cells. This phenomenon was first observed during pathogen infections and vaccinations, where it manifested as enhanced defensive responses in innate immune effector cells-such as those of the mononuclear phagocyte system and natural killer cells-upon re-stimulation. Cancer was a disease with complex mechanisms, marked by the loss of normal growth regulation in cells due to genetic mutations or epigenetic dysregulation, leading to abnormal proliferation and dissemination.
With hundreds of subtypes, cancer could arise in virtually any human tissue or organ. The primary cause of cancer-related mortality was metastasis, which referred to the spread of cancer cells from their original site to distant organs and accounted for approximately 90% of cancer deaths worldwide. The induction of TI involved multiple immune components including myeloid cells, natural killer cells, pattern recognition receptors, and various cytokines.
Notably, the enhanced response observed during secondary stimulation remained non-specific to particular pathogens. Compared to conventional therapeutic approaches, TI demonstrated superior systemic immune activation. Simple pharmacological stimuli such as β-glucan or Bacillus Calmette-Guérin (BCG) not only triggered innate immune responses but also conferred benefits to adaptive immunity, resulting in more rapid immune activation and enhanced efficacy.
TI enhanced the capacity of immune cells to recognize and eliminate cancer cells, playing a critical role in countering metastasis. In this review, we summarized existing knowledge in the field, focusing on the mechanisms underlying TI induction and its significance in combating cancer.
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