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
人类 NK 细胞的泛癌单细胞全景图
英文原题：A pan-cancer single-cell panorama of human natural killer cells.
查看英文原题
A pan-cancer single-cell panorama of human natural killer cells.
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中文摘要
自然杀伤（NK）细胞在抗肿瘤进展的先天免疫应答中发挥着不可或缺的作用。为了描绘其在肿瘤微环境中的表型和功能多样性，我们对来自716例癌症患者、涵盖24种癌症类型的NK细胞进行了整合单细胞RNA测序分析。我们观察到NK细胞组成的异质性具有肿瘤类型特异性。值得注意的是，我们鉴定出一组肿瘤相关NK细胞，它们在肿瘤中富集，表现出受损的抗肿瘤功能，并与不良预后和免疫治疗耐药相关。特定的髓系细胞亚群，尤其是LAMP3+树突状细胞，似乎介导了对NK细胞抗肿瘤免疫的调控。我们的研究为基于NK细胞的癌症免疫提供了见解，并突出了NK细胞亚群作为治疗靶点的潜在临床价值。
展开英文摘要原文
Natural killer (NK) cells play indispensable roles in innate immune responses against tumor progression. To depict their phenotypic and functional diversities in the tumor microenvironment, we perform integrative single-cell RNA sequencing analyses on NK cells from 716 patients with cancer, covering 24 cancer types.
We observed heterogeneity in NK cell composition in a tumor-type-specific manner.
Notably, we have identified a group of tumor-associated NK cells that are enriched in tumors, show impaired anti-tumor functions, and are associated with unfavorable prognosis and resistance to immunotherapy. Specific myeloid cell subpopulations, in particular LAMP3 + dendritic cells, appear to mediate the regulation of NK cell anti-tumor immunity.
Our study provides insights into NK-cell-based cancer immunity and highlights potential clinical utilities of NK cell subsets as therapeutic targets.
论文信息
- 作者
- Tang F、Li J、Qi L、Liu D、Bo Y、Qin S、Miao Y、Yu K
- 第一作者单位
- Biomedical Pioneering Innovation Center (BIOPIC), Academy for Advanced Interdisciplinary Studies, School of Life Sciences, Peking University, Beijing 100871, China.China
- 通讯作者单位
- Biomedical Pioneering Innovation Center (BIOPIC), Academy for Advanced Interdisciplinary Studies, School of Life Sciences, Peking University, Beijing 100871, China; Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen 518132, China. Electronic address: zemin@pku.edu.cn.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Cell2023 Sep 14
- 原文标识
- PubMed 37607536 · DOI 10.1016/j.cell.2023.07.034