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
肿瘤来源的细胞外囊泡 PD-1 通过破坏外周 T 细胞稳态促进肿瘤免疫逃逸
英文原题：Tumor-derived extracellular vesicle PD-1 promotes tumor immune evasion via disruption of peripheral T cell homeostasis.
查看英文原题
Tumor-derived extracellular vesicle PD-1 promotes tumor immune evasion via disruption of peripheral T cell homeostasis.
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中文摘要
程序性细胞死亡1（PD-1）/PD-1配体1（PD-L1）轴介导肿瘤的免疫逃逸，靶向该轴已取得一定的临床获益。免疫细胞中PD-1表达的调控已被充分研究。然而，是否存在其他潜在的免疫细胞表达PD-1的来源仍不清楚。在此，我们报道肿瘤细胞表达PD-1并以细胞外囊泡的形式释放PD-1，后者进入T细胞，并在体外通过PD-L1抑制T细胞功能。在体内，肿瘤细胞来源的细胞外囊泡PD-1通过破坏外周T细胞稳态促进肿瘤生长，表现为脾脏、引流淋巴结和TIL（肿瘤浸润淋巴细胞）中T细胞数量减少和CD8+ T细胞功能受损，而PD-1靶向抗体可恢复上述变化。我们的研究为肿瘤免疫逃逸提供了独特而新颖的视角，并扩展了免疫细胞中PD-1的来源。
展开英文摘要原文
The programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) axis mediates immune evasion of tumor, and targeting this axis has achieved some clinical benefits. The regulation of PD-1 expression in immune cells has been well studied.
However, whether any other potential source of immune cell-expressed PD-1 exists remains unknown.
Here, we report that tumor cells express PD-1 and release PD-1 in the form of extracellular vesicles, which enters T cells and suppresses T cell function via PD-L1 in vitro. In vivo, tumor cell-derived extracellular vesicle PD-1 promotes tumor growth via disrupting peripheral T cell homeostasis, showing by decreased number of T cells and impaired function of CD8 + T cells in spleens, draining lymph nodes and tumor infiltrating lymphocytes, which is restored by PD-1-targeted antibodies.
Our study provides a unique and novel perspective for immune evasion of tumor, and expands a source of PD-1 in immune cells.
论文信息
- 作者
- Wang X、Yang X、Huang C、Liu T、Zang H、Gu Y、Zhang Y、Zhu X
- 第一作者单位
- School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230000, China; Chinese Academy of Sciences (CAS) Key Laboratory of Biomedical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, China; Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Southeast University, Nanjing, 210096, China.China
- 通讯作者单位
- Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Southeast University, Nanjing, 210096, China. Electronic address: gaos@sibet.ac.cn.China
- 期刊
- Cancer letters2025 Mar 1
- 原文标识
- PubMed 39864541 · DOI 10.1016/j.canlet.2025.217486