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
单细胞转录组学揭示胶质母细胞瘤中的免疫抑制微环境并突出肿瘤促进巨噬细胞
英文原题：Single-cell transcriptomics reveals immunosuppressive microenvironment and highlights tumor-promoting macrophage cells in Glioblastoma.
查看英文原题
Single-cell transcriptomics reveals immunosuppressive microenvironment and highlights tumor-promoting macrophage cells in Glioblastoma.
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中文摘要
胶质母细胞瘤（GBM）是成人中最常见且最具侵袭性的原发性脑恶性肿瘤。然而，GBM 微环境（TME）内的细胞异质性和复杂性仍未完全阐明，这构成了开发更有效 GBM 免疫疗法的重大障碍。
在本研究中，我们在单细胞水平上对来自 24 例 GBM 患者的 48 个肿瘤片段进行了整合分析，揭示了免疫浸润细胞中显著的分子多样性。
我们表征了五种不同肿瘤相关巨噬细胞（TAM）亚型的分子特征。值得注意的是，TAM_MRC1 亚型表现出显著的 M2 极化特征。
此外，我们鉴定了一种自然杀伤（NK）细胞亚型，命名为 CD56dim_DNAJB1。该亚型以耗竭表型为特征，表现为应激特征升高以及 PD-L1/PD-1 检查点通路富集。
我们的研究结果还突出了 TME 内恶性胶质瘤细胞、TAM 和 NK 细胞之间显著的细胞间相互作用。总体而言，本研究揭示了 TME 中胶质瘤细胞和免疫细胞的功能异质性，为这种免疫冷肿瘤的治疗干预提供了潜在靶点。
展开英文摘要原文
Glioblastoma (GBM) is the most prevalent and aggressive primary brain malignancy in adults. Nevertheless, the cellular heterogeneity and complexity within the GBM microenvironment (TME) are still not fully understood, posing a significant obstacle in the advancement of more efficient immunotherapies for GBM. In this study, we conducted an integrated analysis of 48 tumor fragments from 24 GBM patients at the single-cell level, uncovering substantial molecular diversity within immune infiltrates.
We characterized molecular signatures for five distinct tumor-associated macrophages (TAMs) subtypes.
Notably, the TAM_MRC1 subtype displayed a pronounced M2 polarization signature.
Additionally, we identified a subtype of natural killer (NK) cells, designated CD56dim_DNAJB1. This subtype is characterized by an exhausted phenotype, evidenced by an elevated stress signature and enrichment in the PD-L1/PD-1 checkpoint pathway.
Our findings also highlight significant cell-cell interactions among malignant glioma cells, TAM, and NK cells within the TME.
Overall, this research sheds light on the functional heterogeneity of glioma and immune cells in the TME, providing potential targets for therapeutic intervention in this immunologically cold cancer.
论文信息
- 作者
- Cheng H、Yan Y、Zhang B、Ma Z、Fu S、Ji Z、Zou Z、Wang Q
- 单位
- Department of Clinical Laboratory, Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Tianjin Huanhu Hospital, Tianjin, China.China
- 期刊
- PloS one2025
- 原文标识
- PubMed 40193323 · DOI 10.1371/journal.pone.0312764
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