Circadian rhythm in immunotherapy and cellular therapy: impacts on the tumor microenvironment

Nov 20, 2025Acta biochimica et biophysica Sinica

Circadian rhythms may affect immunotherapy and cellular therapy in tumors.

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Abstract

Circadian rhythms may influence the effectiveness of immunotherapy in cancer treatment.

Immunotherapy, including cellular therapy, is becoming an important part of cancer care alongside surgery, chemotherapy, and radiotherapy.
Only a limited number of patients respond well to immunotherapy, prompting studies on the tumor microenvironment (TME).
Circadian regulation could affect immune cell behavior and cytokine production within the TME.
Timing of treatments like adoptive cellular therapy and immune checkpoint blockade therapy may improve their effectiveness.
Understanding how circadian rhythms interact with immunotherapy is crucial for enhancing cellular functions in the TME.
Future clinical approaches may incorporate circadian rhythms to boost responses to immunotherapy.

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Immunotherapy, including cellular therapy, has emerged as a crucial pillar in cancer treatment, complementing established modalities such as surgery, chemotherapy and radiotherapy. The clinical observation that immunotherapy is effective in only a limited proportion of patients inspires mechanistic research on the complicated regulatory network within the tumor microenvironment (TME). Circadian regulation significantly affects immune cell behavior, including the activity of immune cells and cytokine production, and emerging evidence suggests the key role of circadian regulation in the TME, which subsequently affects the effectiveness of immunotherapy. Results from preclinical and clinical studies indicate that appropriate timing of adoptive cellular therapy and immune checkpoint blockade therapy improves their efficacy. Therefore, understanding the molecular mechanism of the circadian rhythm together with its role in immunotherapy is essential for optimizing cellular function, proliferation and persistence in the TME. Here, we review how circadian rhythms influence immunotherapy and the TME across different stages of tumor progression. Future clinical protocols may integrate concepts of circadian rhythm and immunotherapy to enhance treatment response.

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Circadian rhythm in immunotherapy and cellular therapy: impacts on the tumor microenvironment

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