Abstract 44P
Background
The process of cancer immunosurveillance is a mechanism of tumor suppression that can protect the host from cancer development throughout its lifetime. 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 growth across murine cancer models.
Methods
In this study, we use mouse melanoma, colon cancer, and breast cancer models to study time-of-day-dependent anti-tumor immune responses. We use immunodeficient mice and animals lacking lineage-specific circadian functions to explore the effect of immune system. We perform similar experiments using human immune cells and retrospectively analyze human vaccination data to study circadian anti-tumor effects in humans.
Results
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 growth. 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 and shows circadian outcomes in both mice and humans.
Conclusions
These data demonstrate that circadian rhythms of anti-tumor immune components are not only critical for the control of tumor growth, but can also be exploited therapeutically.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
European Research Council.
Disclosure
All authors have declared no conflicts of interest.