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:Breast Cancer Disseminated Tumor Cells: Do They Stay and Fight or Run and Hide?
Breast Cancer Disseminated Tumor Cells: Do They Stay and Fight or Run and Hide?
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包括乳腺癌在内的许多实体瘤可能早期播散并进入休眠,即癌细胞在疾病早期扩散,并在长时间内存活而无可检测的生长。这些早期播散的肿瘤细胞有时会重新激活,在原发肿瘤接受根治意图治疗多年乃至数十年后导致无法治愈的转移性疾病。
我们才刚开始了解免疫系统在这一过程中的作用,部分得益于免疫功能完整模型的改进,以及单细胞基因组学和空间转录组学等技术进步。在本期《Cancer Research》中,Bushnell 等人展示了 NK 细胞在这一过程中具有重要作用。作者发现,播散肿瘤细胞和静息细胞表达较高水平的 MHC I,但能抵抗 NK 细胞介导的免疫。提出的机制涉及 STING 通路以及转录因子 Sox2 和 Bach1。鉴于其他研究已强调 T 细胞免疫的重要性,本研究进一步证实免疫系统对肿瘤休眠的调节既重要又多样,并提示未来需进一步厘清机制细节、预测不同类型免疫在何种情况下最为重要。相关论文见 Bushnell 等人,页码 3337。
Many solid tumors including breast cancer can exhibit early dissemination and dormancy-in which cancer cells spread early in the disease process and survive long periods without detectable growth. These early disseminated tumor cells sometimes reactivate and lead to incurable metastatic disease years or even decades after curative-intent therapy for the primary tumor.
We are just beginning to understand the role of the immune system in this process in part because of improvements in immunocompetent models as well as technological advances such as single-cell genomics and spatial transcriptomics. In this issue of Cancer Research, Bushnell and colleagues showed that NK cells are important in this context. The authors found that disseminated tumor cells and quiescent cells express higher levels of MHC 1 but are resistant to NK-cell-mediated immunity.
The proposed mechanism involves the STING pathway and transcription factors Sox2 and Bach1. As other studies have highlighted the importance of T-cell immunity, this work reaffirms the importance and diversity of immune regulation of dormancy and suggests the need for future studies to flesh out mechanistic details and predict when each type of immunity is most important. See related article by Bushnell et al. , p. 3337.
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