Contextual control of CD8⁺ T cell priming by dendritic cell subsets in tumor and inflammatory microenvironments.

IF 7.7 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2026-09-29 DOI:10.1016/j.celrep.2026.118070

Victoria P Schuster, Naomi Berkowitz, Kasidy Brown, Catherine Rousculp, Valentina Laverde, Julia R Unsworth, Megan K Ruhland

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引用次数: 0

Abstract

Migratory and lymph node-resident dendritic cells occupy distinct niches and drive T cell activation during infection, vaccination, and cancer. How tissue context and dendritic cell subset-specific transcriptional programs integrate to shape CD8⁺ T cell priming remains incompletely defined. Using fluorescent antigen, we track antigen distribution, dendritic cell transcriptional programming, and cross-presentation across tumor, inflamed, and steady-state tissues. Tumor antigen is more widely distributed among lymph node dendritic cells than skin-derived antigen. Migratory type 1 dendritic cells display higher expression of cross-presentation machinery and superior per-cell cross-presentation and induction of CD8⁺ T cell proliferation compared to lymph node-resident type 1 dendritic cells. Ultimately, antigen access and cell-specific cross-presentation efficiency together predict the quality of CD8⁺ T cell priming. These results identify migratory type 1 dendritic cells as central mediators of antitumor CD8⁺ T cell responses and support therapeutic strategies that augment the efficiency of resident dendritic cell cross-presentation.

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肿瘤和炎症微环境中树突状细胞亚群对CD8+ T细胞启动的上下文控制。

迁移和淋巴结驻留的树突状细胞占据不同的生态位，并在感染、疫苗接种和癌症期间驱动T细胞激活。组织环境和树突状细胞亚群特异性转录程序如何整合形成CD8+ T细胞启动仍未完全确定。使用荧光抗原，我们跟踪抗原分布，树突状细胞转录编程，以及肿瘤，炎症和稳态组织的交叉呈现。肿瘤抗原在淋巴结树突状细胞中的分布比皮肤源性抗原更广泛。与淋巴结驻留型1型树突状细胞相比，迁移型1型树突状细胞表现出更高的交叉呈递机制表达和更优越的细胞间交叉呈递和诱导CD8+ T细胞增殖。最终，抗原通路和细胞特异性交叉呈递效率共同预测CD8+ T细胞启动的质量。这些结果确定了迁移型1型树突状细胞是抗肿瘤CD8+ T细胞反应的中心介质，并支持了增强常驻树突状细胞交叉呈递效率的治疗策略。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.