Synchronizing immunity with time: unlocking the potential of chrono-immunotherapy in cancer

Circadian rhythms, an endogenous timing system that enables organisms to adapt to Earth's rotation, profoundly regulate fundamental physiological processes including cellular metabolism, hormone secretion, and immune surveillance. Recent advances have revealed that circadian disruption drives tumor initiation and progression, with its modulatory role in tumor immunity serving as a pivotal link between basic chronobiology and clinical oncology. Building upon an overview of circadian concepts and molecular regulatory mechanisms, this review synthesizes the multidimensional influence of circadian rhythms on tumor immunity, encompassing the temporal dynamics of immune cell proliferation, migration, and activation, remodeling of the tumor immune microenvironment, and the rhythmic regulation of immune checkpoint molecule expression. Furthermore, we examine ongoing efforts and remaining challenges in chronotherapy-based approaches to cancer immunotherapy. This review highlights that the intersection of circadian rhythms and cancer immunotherapy is transitioning from proof-of-concept studies to clinical implementation, ushering in a new paradigm that considers not only the timing of treatment but also the optimization of therapeutic timing.