小柯机器人

瑞士日内瓦大学Christoph Scheiermann团队近期取得重要工作进展，他们研究发现树突状细胞指导昼夜节律的抗肿瘤免疫反应。相关研究成果2022年12月5日在线发表于《自然》杂志上。

据介绍，癌症免疫监管的过程是抑制肿瘤的一种机制，可以保护宿主在其一生中不发生癌症。然而，它的有效性是否会在一天内发生波动，目前还不清楚。

研究人员发现，在小鼠癌症模型中，肿瘤植入的最初时间决定了随后的肿瘤大小。使用免疫缺陷小鼠和缺乏谱系特异性昼夜节律功能的动物，研究人员发现，树突状细胞（DC）和CD8⁺ T细胞发挥昼夜节律抗肿瘤功能，控制黑色素瘤的体积。DC向肿瘤引流淋巴结（dLN）的节律性运输控制着肿瘤抗原特异性CD8⁺ T细胞的昼夜节律反应，这取决于共刺激分子CD80的昼夜节律表达。因此，当与DC功能同步时，癌症免疫治疗将更有效，在小鼠中显示出昼夜节律的结果，并表明在人类中也有类似的效果。

这些数据表明，抗肿瘤免疫成分的昼夜节律不仅对控制肿瘤的大小至关重要，而且还可以在肿瘤治疗上加以利用。

附：英文原文

Title: Dendritic cells direct circadian anti-tumor immune responses

Author: Wang, Chen, Barnoud, Coline, Cenerenti, Mara, Sun, Mengzhu, Caffa, Irene, Kizil, Burak, Bill, Ruben, Liu, Yuanlong, Pick, Robert, Garnier, Laure, Gkountidi, Olga A., Ince, Louise M., Holtkamp, Stephan, Fournier, Nadine, Michielin, Olivier, Speiser, Daniel E., Hugues, Stphanie, Nencioni, Alessio, Pittet, Mikal J., Jandus, Camilla, Scheiermann, Christoph

Issue&Volume: 2022-12-05

Abstract: The process of cancer immunosurveillance is a mechanism of tumor suppression that can protect the host from cancer development throughout its lifetime1,2. Yet, it is unknown whether its effectiveness fluctuates over a single day. Here, we demonstrate that the initial time-of-day of tumor engraftment dictates ensuing tumor size across murine cancer models. Using immunodeficient mice and animals lacking lineage-specific circadian functions, we show that dendritic cells (DCs) and CD8+ T cells exert circadian anti-tumor functions that control melanoma volume. Specifically, we find that rhythmic trafficking of DCs to the tumor draining lymph node (dLN) governs a circadian response of tumor antigen-specific CD8+ T cells, which is dependent on circadian expression of the co-stimulatory molecule CD80. Consequently, cancer immunotherapy is more effective when synchronized with DC functions, shows circadian outcomes in mice and suggests similar effects in humans. These data demonstrate that circadian rhythms of anti-tumor immune components are not only critical for the control of tumor size but can also be exploited therapeutically.

DOI: 10.1038/s41586-022-05605-0

Source: https://www.nature.com/articles/s41586-022-05605-0

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html