树突状细胞表达 CD5 指导 T 细胞免疫并维持免疫治疗反应。
CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses.
机构信息
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Molecular Cell and Developmental Biology at University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
出版信息
Science. 2023 Feb 17;379(6633):eabg2752. doi: 10.1126/science.abg2752.
Abstract
The induction of proinflammatory T cells by dendritic cell (DC) subtypes is critical for antitumor responses and effective immune checkpoint blockade (ICB) therapy. Here, we show that human CD1cCD5 DCs are reduced in melanoma-affected lymph nodes, with CD5 expression on DCs correlating with patient survival. Activating CD5 on DCs enhanced T cell priming and improved survival after ICB therapy. CD5 DC numbers increased during ICB therapy, and low interleukin-6 (IL-6) concentrations promoted their de novo differentiation. Mechanistically, CD5 expression by DCs was required to generate optimally protective CD5 T helper and CD8 T cells; further, deletion of CD5 from T cells dampened tumor elimination in response to ICB therapy in vivo. Thus, CD5 DCs are an essential component of optimal ICB therapy.
摘要
树突状细胞（DC）亚型诱导前炎症性 T 细胞对于抗肿瘤反应和有效的免疫检查点阻断（ICB）治疗至关重要。在这里，我们表明，在黑色素瘤受累的淋巴结中，人 CD1cCD5 DC 减少，并且 DC 上的 CD5 表达与患者的存活相关。在 DC 上激活 CD5 增强了 T 细胞的启动，并改善了 ICB 治疗后的存活。在 ICB 治疗期间，CD5 DC 的数量增加，并且低白细胞介素 6（IL-6）浓度促进其从头分化。从机制上讲，DC 上的 CD5 表达对于产生最佳保护性 CD5 T 辅助和 CD8 T 细胞是必需的；此外，从 T 细胞中删除 CD5 会抑制体内 ICB 治疗对肿瘤消除的作用。因此，CD5 DC 是最佳 ICB 治疗的重要组成部分。
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3
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4
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5
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Mol Ther Oncolytics. 2021 Aug 6;22:307-325. doi: 10.1016/j.omto.2021.07.008. eCollection 2021 Sep 24.
6
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Genome Res. 2021 Nov;31(11):2120-2130. doi: 10.1101/gr.275607.121. Epub 2021 Aug 18.
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BMC Cancer. 2021 Jul 3;21(1):767. doi: 10.1186/s12885-021-08536-7.
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