免疫监视
启动(农业)
抗原提呈细胞
T细胞
免疫系统
免疫学
癌症免疫疗法
树突状细胞
生物
免疫疗法
交叉展示
抗原呈递
背景(考古学)
抗原
癌症研究
植物
发芽
古生物学
作者
Devanshi A Nayak,Abigail L. Sedlacek,Anthony R. Cillo,Simon C. Watkins,Robert Binder
出处
期刊:Cancer immunology research
[American Association for Cancer Research]
日期:2024-09-13
标识
DOI:10.1158/2326-6066.cir-24-0326
摘要
Abstract During cancer immunosurveillance, dendritic cells (DCs) play a central role in orchestrating T-cell responses against emerging tumors. Capture of miniscule amounts of antigen along with tumor-initiated costimulatory signals can drive maturation of DCs. Expression of CD91 on DCs is essential in cross-priming of T-cell responses in the context of nascent tumors. Multiple DC and macrophage subsets express CD91 and engage tumor-derived gp96 to initiate antitumor immune responses, yet the specific CD91+ antigen-presenting cells (APCs) that are required for T-cell cross-priming during cancer immunosurveillance are unknown. In this study, we determined that CD91 expression on type 1 conventional DCs (cDC1) is necessary for cancer immunosurveillance. Specifically, CD91-expressing cDC1 were found to capture the CD91 ligand gp96 from tumors and, upon migration to the lymph nodes, distribute gp96 among lymph-node resident APCs. However, cDC1 that captured tumor-derived gp96 only provided early tumor control, while sustained and long-term tumor rejection was bestowed to the host by other gp96+ cross-priming DCs. We further found that the CD91-induced transcriptome in APCs promoted cross-priming of T-cell responses while downregulating immune regulatory pathways. Our results show an elaborate and synchronized division of labor of APCs in the successful elimination of cancer cells via CD91. We predict that the specialized functions of APC subsets can be harnessed for immunotherapy of disease.
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