Temporal Immune Surveillance in Cancer: A Circadian Framework from Mechanisms to Chronotherapeutic Integration

From a traditional perspective, "immune surveillance" has long been regarded as a static process. However, recent studies have shown that the immune system's ability to detect and combat tumors is dynamically regulated by circadian rhythms; we define this concept as "temporal immune surveillance". Disruption of circadian rhythms leads to impaired immune surveillance, thereby creating an immunosuppressive microenvironment that favors the development and progression of cancer. We describe a multi-tiered regulatory network encompassing the intrinsic circadian clocks of immune cells, clock-mediated regulation of immune gene networks, and finally, systemic regulation via the neuro-immune and microbiota-immune axes. These findings pave the way for chrono-immunotherapy, a strategy built on three integrated pillars: optimizing the timing of existing therapies (e.g., immune checkpoint inhibitors), pharmacologically reprogramming disrupted circadian clocks, and pre-synchronizing host physiology through lifestyle interventions such as time-restricted eating. Developing circadian biomarkers and personalized chronotherapy regimens is crucial for advancing precision oncology.