Archives of toxicologyJul 9, 2026

Links between the body’s daily clock, cell damage from oxidation, and cancer’s ability to weaken the immune system

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jul 10, 2026

Abstract

Circadian rhythm disruption may promote immunosuppression by reducing cytotoxic CD8⁺ T cell infiltration.

Circadian rhythm and oxidative stress are interrelated factors that influence cancer progression and immune response.
Disruption of the circadian rhythm leads to an increase in immunosuppressive cells, such as regulatory T cells and myeloid-derived suppressor cells.
Oxidative stress can polarize macrophages towards an M2 phenotype, enhancing immunosuppression while also having the potential to disrupt immunosuppressive networks.
Circadian rhythm disruption results in the accumulation of reactive oxygen species (ROS), which may recruit immunosuppressive cells and upregulate immune checkpoints like PD-L1.
Circadian rhythm could serve as a prognostic biomarker and may enhance the effectiveness of chrono-immunotherapy, which aligns treatment timing with biological rhythms.

Simplified

Circadian rhythm and oxidative stress are fundamental biological regulators whose intricate interplay plays a pivotal role in cancer progression and immunosuppression. These two factors engage in a bidirectional, self-reinforcing pathological loop that drives tumor progression and fosters an immunosuppressive tumor microenvironment. In the context of cancer, circadian rhythm disruption promotes immunosuppression by reducing cytotoxic CD8⁺ T cell infiltration while expanding populations of immunosuppressive cells such as regulatory T cells and myeloid-derived suppressor cells. Oxidative stress acts as a pivotal effector with dual roles, it promotes immunosuppression by polarizing macrophages toward an M2 phenotype, yet it is also strategically harnessed to disrupt immunosuppressive networks. Critically, oxidative stress serves as a central link, wherein circadian rhythm disruption, through the accumulation of ROS, drives the recruitment of immunosuppressive cells and upregulates immune checkpoints such as PD-L1, thereby suppressing anti-tumor immunity. Furthermore, emerging evidence highlights the potential of circadian rhythm as a prognostic biomarker and underscores the promise of chrono-immunotherapy, which strategically times interventions to align with the circadian rhythm to optimize anti-tumor immune function. Collectively, the circadian rhythm and redox balance represent novel therapeutic targets, with pharmacological agents that restore circadian rhythm and enable cell-selective modulation of oxidative stress. Thus, integrating circadian rhythm and oxidative stress into oncology offers a promising strategy to improve cancer prevention, prognosis, and treatment outcomes.

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Declarations. Conflict of interest: 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.

PubMed

Links between the body’s daily clock, cell damage from oxidation, and cancer’s ability to weaken the immune system

Abstract

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Competing interests

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Abstract

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