Like sleeping and waking up, the immune system is under circadian control and exhibits a time-of-day dependent response to threat encounter. Cancer, which is caused by the capacity of abnormal cancer cells to escape the surveillance of our immune system, is such a threat. Until today, little was known about how day and night rhythms regulate the immune system in cancer. Therefore, the aim of Chen Wang, Coline Barnoud and their team was to learn more about the influence of the circadian rhythm on cancer immunosurveillance.

The scientists engrafted tumour cells of various tumour models into mice at different times of the day. They then quantified tumour growth as well as immune cells in the tumour and lymph nodes to determine the importance of different immune cell subsets. Finally, they performed chrono-immunotherapy experiments to evaluate the effect of anti-tumour vaccination in dependence of time-of day.

They demonstrated that the tumours grew faster when engrafted into mice during their active phase (in the night/dark period) compared to their resting phase (in the day/light period).

This is true across different cancer types, including melanoma, breast cancer, and colon cancer. Specifically, more defence cells like dendritic cells and T-cells were present during the resting phase in the draining lymph nodes. Also, the molecule CD80 is controlled by the circadian rhythm, which further enhances the anti-tumour immune response. Lastly, in mice, vaccination in the resting phase can reduce tumour size by 50% compared to active phase vaccination. In humans, morning anti-tumour vaccination is 5-fold more efficient than afternoon vaccination in terms of triggering tumour-specific CD8 T-cell responses.

These remarkable results show for the first time that the response of the immune system to tumour challenges is under circadian control. Therefore, they highlight the importance of considering the time of day for the administration of treatments involving the activation of the immune system to improve the patients’ clinical outcome.

Dendritic cells direct circadian anti-tumour immune responses. Chen Wang, Coline Barnoud, Mara Cenerenti, Mengzhu Sun, Irene Caffa, Burak Kizil, Ruben Bill, Yuanlong Liu, Robert Pick, Laure Garnier, Olga A. Gkountidi, Louise M. Ince, Stephan Holtkamp, Nadine Fournier, Olivier Michielin, Daniel E. Speiser, Stéphanie Hugues, Alessio Nencioni, Mikaël J. Pittet, Camilla Jandus, Christoph Scheiermann. Nature. 2023 Feb;614(7946):136-143