CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
基于 IDH 状态剖析胶质瘤免疫微环境：对免疫治疗的启示
英文原题：Dissecting the Immunological Microenvironment of Glioma Based on IDH Status: Implications for Immunotherapy.
查看英文原题
Dissecting the Immunological Microenvironment of Glioma Based on IDH Status: Implications for Immunotherapy.
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中文摘要
胶质瘤，尤其是IDH野生型胶质瘤，与不良预后相关，但其免疫学景观仍不确定。我们分析了55例胶质瘤患者的RNA测序数据，使用CIBERSORTx估计免疫浸润，并通过Ecotyper分析免疫细胞状态。与IDH突变型胶质瘤相比，IDH野生型胶质瘤显示出显著更高的免疫细胞浸润（p = 0.002），尤其是调节性T细胞（Tregs）和巨噬细胞，以及更高比例的耗竭T细胞。基于免疫特征的聚类揭示了两个组。Cluster A富含IDH野生型病例，表现出免疫浸润增强，但同时也有明显的免疫抑制。Cluster B包括IDH野生型和突变型病例，显示出较低的免疫浸润水平。从IDH野生型肿瘤培养的TIL（肿瘤浸润淋巴细胞）在抗PD-1、CSF1R抑制剂或STAT3抑制剂处理后表现出有限的扩增，没有明显的聚类特异性差异。肿瘤反应性TIL主要见于Cluster A。这些发现强调，IDH野生型胶质瘤具有免疫抑制和异质性微环境，可能限制对单药免疫疗法的反应。一种针对多种免疫抑制机制的个性化、多靶点方法可能对于改善这一侵袭性胶质瘤亚组的免疫治疗结果至关重要。
展开英文摘要原文
Gliomas, particularly IDH-wildtype ones, are associated with poor prognosis, yet their immunological landscape remains uncertain.
We analyzed RNA sequencing data from 55 glioma patients, estimating immune infiltration with CIBERSORTx and immune cell states via Ecotyper. IDH-wildtype gliomas showed significantly higher immune cell infiltration ( p = 0. 002), notably of regulatory T cells (Tregs) and macrophages, and a greater proportion of exhausted T cells compared to IDH-mutant gliomas. Clustering based on immune profiles revealed two groups.
Cluster A, enriched for IDH-wildtype cases, exhibited heightened immune infiltration but also marked immunosuppression. Cluster B, which included both IDH-wildtype and mutant cases, showed lower levels of immune infiltration. Tumor-infiltrating lymphocyte (TIL) cultured from IDH-wildtype tumors demonstrated limited expansion following anti-PD-1, a CSF1R inhibitor, or a STAT3 inhibitor treatment, without clear cluster-specific differences. Tumor-reactive TILs were mainly observed in cluster A.
These findings highlight that IDH-wildtype gliomas have an immunosuppressive and heterogeneous microenvironment, potentially limiting responses to single-agent immunotherapies. A personalized, multi-targeted approach addressing multiple immunosuppressive mechanisms may be essential to improve immunotherapy outcomes in this aggressive glioma subgroup.
论文信息
- 作者
- Kikuchi M、Takami H、Kobayashi Y、Nagaoka K、Kitagawa Y、Nomura M、Takayanagi S、Tanaka S
- 第一作者单位
- Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.Japan
- 通讯作者单位
- Department of Immunology, Kindai University Faculty of Medicine, Osakasayama 589-8511, Osaka, Japan.Japan
- 期刊
- Cells2025 Jul 7
- 原文标识
- PubMed 40643554 · DOI 10.3390/cells14131035
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