Dendritic Cells Direct Circadian Anti‐Tumor Immune Response

Circadian time partitioning of the day is a ubiquitous feature of physiological processes. Recent observations demonstrate that the initial time of the day when an inflammatory stimulus is encountered by the host governs the strength of the ensuing immune response. This is the case for an acute setting, which is mainly driven by innate immunity but also for adaptive immunity, where the effect is observed even weeks later. Here, we demonstrate a clear effect of time-of-day of tumor engraftment on tumor growth. Using immunocompromised NSG as well as Rag2-deficient mice we can trace this difference to the adaptive arm of the immune response. More specifically, rhythmicity in the anti-tumor response is abrogated in mice exhibiting lineage-specific loss of circadian rhythmicity in T cells or dendritic cells (DCs). Using chronotherapy and rhythmic targeting of tumors with DC vaccines reduces tumor burden in a time-of-day dependent manner. Together, these data indicate that a circadian immune system can control tumor growth.