Dendritic cells direct circadian anti-tumour immune responses.
Dendritic cells direct circadian anti-tumour immune responses.
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DOI：
10.1038/s41586-022-05605-0
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发表时间：
2023-03
影响因子：
50.5
通讯作者：
Scheiermann, C.
中科院分区：
文献类型：
--
作者：
Wang, C.;Barnoud, C.;Kizil, B.;Scheiermann, C.
癌症免疫监测的过程是肿瘤抑制的机制，可以保护宿主在其一生中免受癌症的发展。然而，尚不清楚癌症免疫监视的有效性是否在一天中会波动。在这里，我们证明了肿瘤植入一天中的初始时间决定了小鼠癌模型的随之而来的肿瘤大小。使用免疫缺陷的小鼠以及缺乏谱系特异性昼夜节律功能的小鼠，我们表明树突状细胞（DCS）和CD8+ T细胞会散发出控制黑色素瘤体积的昼夜节律抗肿瘤功能。具体而言，我们发现DC对肿瘤淋巴结的节奏运输控制肿瘤 - 抗原特异性CD8+ T细胞的昼夜节律，该反应取决于共刺激分子CD80的昼夜节律表达。因此，当与直流功能同步时，癌症免疫疗法更有效，显示出小鼠的昼夜节律结果，并暗示了对人类的类似作用。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大小至关重要，而且还具有治疗性相关性。
树突状细胞对肿瘤排出淋巴结的节奏运输控制肿瘤 - 抗原特异性CD8+ T细胞的昼夜节律反应，该反应取决于共刺激分子CD80的昼夜节律表达。
The process of cancer immunosurveillance is a mechanism of tumour suppression that can protect the host from cancer development throughout its lifetime. However, it is unknown whether the effectiveness of cancer immunosurveillance fluctuates over a single day. Here we demonstrate that the initial time of day of tumour engraftment dictates the ensuing tumour size across mouse cancer models. Using immunodeficient mice as well as mice lacking lineage-specific circadian functions, we show that dendritic cells (DCs) and CD8+ T cells exert circadian anti-tumour functions that control melanoma volume. Specifically, we find that rhythmic trafficking of DCs to the tumour draining lymph node governs a circadian response of tumour-antigen-specific CD8+ T cells that is dependent on the circadian expression of the co-stimulatory molecule CD80. As a consequence, 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 the circadian rhythms of anti-tumour immune components are not only critical for controlling tumour size but can also be of therapeutic relevance. Rhythmic trafficking of dendritic cells to the tumour draining lymph node governs a circadian response of tumour-antigen-specific CD8+ T cells that is dependent on the circadian expression of the co-stimulatory molecule CD80.