The circadian architecture of tumor immunity: mechanistic insights and treatment strategies

BACKGROUND: The circadian clock orchestrates many key physiological processes related to anti-tumor immunity, including the cell cycle, energy metabolism, immune infiltration, and cytokine secretion. Increasing evidence suggests that circadian clock disruption is involved in tumorigenesis and tumor progression. Both clinical and basic research indicate that the circadian clock is a central regulator of tumor immunity and an important target for intervention. However, the role of the circadian clock in remodeling tumor immunity, as well as existing and potential intervention strategies, remains largely uncharacterized. MAIN: To investigate the role of the circadian clock in tumor immunity, we integrated a tumor-related circadian regulatory framework encompassing the central pacemaker, peripheral cell-autonomous clocks, and environmental and behavioral factors such as sleep and feeding. Evidence from epidemiological, clinical, and translational studies reveals that circadian disruption impairs immune surveillance and promotes tumor initiation and progression, contributing to increased cancer risk and poorer outcomes. We further examine the mechanisms by which circadian dysregulation reshapes the tumor immune microenvironment and alters both innate and adaptive antitumor immunity. Finally, we discuss emerging therapeutic approaches that leverage circadian biology to enhance antitumor immune responses, including circadian clock-targeting interventions and chronotherapy, highlighting their potential to improve cancer treatment outcomes. CONCLUSION: Evidence reviewed here indicates that circadian dysregulation promotes tumor progression through cell-intrinsic clock reprogramming and remodeling of the tumor immune microenvironment. By regulating immune surveillance, metabolic homeostasis, and the function of both immune effector and immunoregulatory cells, the circadian clock plays a central role in antitumor immunity. These findings support the integration of chronotherapy and circadian clock-targeting strategies with immunotherapy to improve the precision and efficacy of cancer treatment.