image: ICI therapy can be optimized by leveraging circadian rhythms and tumor microenvironment characteristics through four main strategies: (1) Optimizing the timing of ICI administration to the early morning or active phases based on circadian patterns; (2) Combining therapies targeting key immune cells, receptors, and cytokines in the tumor microenvironment; (3) Implementing chronobiological interventions including small molecule agonists (RORγ, REV-ERBα/β, CRY), hormone modulation, and non-pharmacological approaches; (4) Personalizing treatment based on individual circadian profiles.
Credit: Anqi Lin, Xiuhui Fang, Bufu Tang, Peng Luo
Researchers have discovered that the body’s internal clock—the circadian rhythm—may hold the key to improving the success of cancer immunotherapy. In a new review published in Journal of the National Cancer Center, scientists from Donghai County People's Hospital, Zhujiang Hospital, and several national research centers provide the first integrated overview of how circadian regulation shapes the tumor microenvironment (TME) and determines patients’ responses to immune checkpoint blockade therapies.
Immune checkpoint inhibitors (ICIs), which target PD-1, PD-L1, or CTLA-4, have revolutionized cancer treatment but show variable success among patients. The study reveals that circadian rhythms—the 24-hour cycles governing biological processes—profoundly affect tumor growth, immune cell activity, angiogenesis, and metabolism within the TME. Disruption of these rhythms can suppress immune responses, promote tumor progression, and diminish ICI efficacy.
“Circadian regulation is a critical yet underappreciated factor influencing how tumors interact with the immune system,” said corresponding author Dr. Peng Luo. “By aligning immunotherapy with the body’s natural rhythms, we may significantly enhance treatment outcomes.”
The authors highlight that time-dependent fluctuations in immune cell infiltration, checkpoint molecule expression, and drug metabolism create daily “windows” of therapeutic opportunity. Clinical data already suggest that patients receiving immunotherapy in the morning experience improved survival compared to those treated later in the day.
The review also explores emerging strategies such as targeting circadian genes (like BMAL1, PER, and ROR) to reshape the tumor microenvironment, combining chronotherapy with ICI treatment, and integrating multi-omics and AI-driven models to design personalized dosing schedules. These findings mark a new frontier in precision oncology known as “chronomedicine.”
“Our work provides a theoretical foundation for synchronizing cancer treatment with biological time,” said first author Dr. Anqi Lin. “Optimizing the timing of immunotherapy could transform patient care from one-size-fits-all to truly individualized.”
This research bridges molecular chronobiology and cancer immunotherapy, emphasizing the importance of integrating temporal dynamics into future clinical trials. The authors call for large-scale, multi-center studies to establish standardized frameworks for time-based cancer treatment.
Journal
Journal of the National Cancer Center
Method of Research
Literature review
Article Title
Temporal Dynamics in Cancer Immunotherapy: The Interplay Between Circadian Rhythms, Tumor Microenvironment, and Immune Checkpoint Blockade
Article Publication Date
25-Nov-2025
COI Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.