树突状细胞中ERα阻断增强抗原交叉呈递并诱导抗肿瘤CD8 T细胞免疫
{"_":"ERα blockade in dendritic cells enhances antigen cross-presentation and induces antitumor CD8 T cell immunity.","sup":["+"]}
摘要(中文译文)
树突状细胞（DC）功能障碍会阻碍抗肿瘤免疫，因此理解DC抗原呈递的内在调控因子以及由此引发的抗肿瘤CD8 T细胞激活，可能有益于治疗。在此，我们利用全基因组CRISPR筛选DC中调控抗原呈递的基因，并鉴定出雌激素受体α（ERα）是一种抑制抗原交叉呈递的内在检查点。ERα的基因组缺失或药理学降解可增强小鼠和人类DC中的抗原呈递及CD8 T细胞致敏。在机制上，ERα不依赖经典雌激素信号，而是维持Galectin-3介导的CHMP4b向受损吞噬体的募集，从而促进ESCRT-III介导的膜修复并限制胞质抗原转位。在体内，ERα缺陷或ERα降解的DC疫苗可扩增肿瘤特异性CD8 T细胞，从而抑制皮下肿瘤小鼠的肿瘤生长。在体外，FDA批准的ERα拮抗剂可增强人DC介导的抗原特异性人CD8 T细胞激活。因此，我们的工作揭示了ERα在吞噬体完整性中的非经典作用，即作为DC中抗原交叉呈递的检查点，并提示靶向ERα的DC疫苗作为一种潜在的免疫治疗策略。
Abstract
Dendritic cells (DC) dysfunction impedes antitumor immunity, so understanding intrinsic regulators of DC antigen presentation and the resulting activation of antitumor CD8 T cells could benefit therapy. Here, we use a genome-wide CRISPR screen for antigen presentation-regulating genes in DCs, and identify estrogen receptor α (ERα) as an intrinsic checkpoint inhibiting antigen cross-presentation. ERα genomic deficiency or pharmacological degradation enhances antigen presentation and CD8 T cell priming in mouse and human DCs. Mechanistically, independently of canonical estrogen signaling, ERα sustains Galectin-3-mediated recruitment of CHMP4b to damaged phagosomes, thereby facilitating ESCRT-III-mediated membrane repair and restricting cytosolic antigen translocation. In vivo, ERα-deficient or ERα-degraded DC vaccines expand tumor-specific CD8 T cells to suppress tumor growth in mice bearing subcutaneous cancers. In vitro, FDA-approved ERα antagonists enhance human DC-mediated activation of antigen-specific human CD8 T cells. Our work thus uncovers a non-canonical role of ERα in phagosome integrity as a checkpoint for antigen cross-presentation in DCs, and implicates ERα-targeted DC vaccines as a potential immunotherapeutic strategy.
如何引用
AMA
Yaxin Liu, Zhongfei Ma, Xuelian Li, Yuanyuan Ding, Zhiqing Li, Bin Zhang, et al. {"_":"ERα blockade in dendritic cells enhances antigen cross-presentation and induces antitumor CD8 T cell immunity.","sup":["+"]}. Nature communications. 2026; doi:10.1038/s41467-026-72647-7.
APA
Yaxin Liu, Zhongfei Ma, Xuelian Li, Yuanyuan Ding, Zhiqing Li, Bin Zhang, et al (2026). {"_":"ERα blockade in dendritic cells enhances antigen cross-presentation and induces antitumor CD8 T cell immunity.","sup":["+"]}. Nature communications. https://doi.org/10.1038/s41467-026-72647-7
GB/T 7714
Yaxin Liu, Zhongfei Ma, Xuelian Li, Yuanyuan Ding, Zhiqing Li, Bin Zhang, et al. {"_":"ERα blockade in dendritic cells enhances antigen cross-presentation and induces antitumor CD8 T cell immunity.","sup":["+"]}[J]. Nature communications, 2026 doi:10.1038/s41467-026-72647-7.
在 PubMed增强版 阅读全文
翻译全文 · AI 文献问答 · PDF 原文下载 · 引用导出