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高效生成人类 cDC1 样细胞,通过 CD4(+) T 细胞辅助来检测并增强肿瘤反应性 T 细胞

英文原题:Efficient generation of human cDC1-like cells to detect and enhance tumor-reactive T cells via CD4(+) T cell help.

查看英文原题

Efficient generation of human cDC1-like cells to detect and enhance tumor-reactive T cells via CD4(+) T cell help.

PubMed 2026/07/22(内容时间) Cell Rep Methods Q1 · IF 5.8(JCR 2025)

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中文摘要

经典1型树突状细胞(cDC1s)通过交叉呈递肿瘤抗原并致敏细胞毒性CD8+ T淋巴细胞(CTLs),在抗肿瘤免疫中发挥关键作用。经CD4+T细胞辅助获得的许可使cDC1s具有增强的交叉呈递和CTL致敏能力,使其成为改善过继性T细胞疗法的有前景的工具。然而,原代人cDC1s的稀缺限制了其深入的转化研究和应用。在此,我们描述了一种从非动员外周血中CD34+c-KIT+祖细胞在体外高效生成DCs的方法。该DC群体富集cDC1样细胞,这些细胞通过上调参与抗原交叉呈递和T细胞共刺激的关键分子来响应CD4+T细胞辅助。在CD4+T细胞介导的许可下,祖细胞来源的DC促进肿瘤特异性CTL致敏,并有助于检测血液和肿瘤组织中罕见的肿瘤抗原特异性CD8+T细胞。这一整合了CD4+T细胞辅助的DC培养平台为癌症中的免疫监测和优化过继性T细胞疗法提供了一个可扩展的系统。

展开英文摘要原文

Classical type 1 dendritic cells (cDC1s) are crucial to anti-tumor immunity by cross-presenting tumor antigens and priming cytotoxic CD8 + T lymphocytes (CTLs). Licensing via CD4 + T cell help endows cDC1s with enhanced cross-presentation and CTL-priming capacity, making them a promising tool to improve adoptive T cell therapies.

However, the scarcity of primary human cDC1s limits their in-depth translational investigation and application.

Here, we describe a method to efficiently generate DCs in vitro from CD34 + c-KIT + progenitors in non-mobilized peripheral blood. This DC population is enriched for cDC1-like cells that respond to CD4 + T cell help by upregulation of key molecules involved in antigen cross-presentation and T cell costimulation.

Upon CD4 + T cell-mediated licensing, the progenitor-derived DC promotes tumor-specific CTL priming and facilitates detection of rare tumor antigen-specific CD8 + T cells in blood and tumor tissues. This DC culture platform incorporating CD4 + T cell help provides a scalable system for immunomonitoring and optimizing adoptive T cell therapies in cancer.

论文信息

作者
Wang Y、Lei X、de Wit T、Schrama E、Welters MJP、van Leeuwen K、de Kivit S、de Boer M
第一作者单位
Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands.Netherlands
通讯作者单位
Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: y.xiao@lumc.nl.Netherlands
期刊
Cell reports methods2026 Sep 21
原文标识
PubMed 42486103 · DOI 10.1016/j.crmeth.2026.101533