Zhang, Z., Zeng, P., Gao, W. et al. Circadian clock: a regulator of the immunity in cancer. Cell Commun Signal 19, 37 (2021). https://doi.org/10.1186/s12964-021-00721-2


The circadian clock is an endogenous timekeeper system that controls and optimizes biological processes, which are consistent with a master circadian clock and peripheral clocks and are controlled by various genes. Notably, the disruption of circadian clock genes has been identified to affect a wide range of ailments, including cancers. The cancer-immunity cycle is composed of seven major steps, namely cancer cell antigen release and presentation, priming and activation of effector immunity cells, trafficking, and infiltration of immunity to tumors, and elimination of cancer cells. Existing evidence indicates that the circadian clock functions as a gate that govern many aspects of the cancer-immunity cycle. In this review, we highlight the importance of the circadian clock during tumorigenesis, and discuss the potential role of the circadian clock in the cancer-immunity cycle. A comprehensive understanding of the regulatory function of the circadian clock in the cancer-immunity cycle holds promise in developing new strategies for the treatment of cancer.



Disruption of the circadian clock contributes to cancer

Over the past years, studies have shown that disruption of the circadian rhythm contributes to the incidence and development of various cancer [4950]. Previous studies have revealed that shift work is implicated in tumorigenesis [5152]. Women who work at night instead of days exhibit an approximately 10% increased risk of breast cancer [53,54,55].

Of note, the disruption of life cycle oscillation causes the increase of spontaneous cancer in chronic jet-lag mouse model. For example, Minami et al. discussed that chronic jet-lag mice showed the short lifespan, splenomegaly, and the accelerated development of liver cancer [57]. In addition, the chrono-disruption of the circadian clock is crucial in metabolic and immunologic changes and is implicated in non-alcoholic fatty liver disease/nonalcoholic steato-hepatitis/hepatocellular cancer [58].

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