Central OC Times

A multidisciplinary research team at the University of California, Irvine has discovered that the circadian clock can be utilized to enhance the efficacy of checkpoint inhibitor cancer therapy. This biological pacemaker governs daily rhythms in physiological processes, including immune functions. The study, published in Nature Immunology, highlights the potential of optimizing time-of-day delivery based on individual circadian patterns for improved prevention and treatment.

"Disruption of the internal biological pacemaker is an inherent aspect of modern society that may contribute to the rising incidence of many cancer types," said Selma Masri, UC Irvine associate professor of biological chemistry and corresponding author. "We found that proper regulation of circadian rhythms is necessary to suppress inflammation and support peak immune function."

Using advanced single-cell RNA sequencing in a genetic model of colorectal cancer, researchers identified clock-dependent changes controlling myeloid-derived cells that suppress T cell activation. They found that disruption in epithelial cells lining the intestine alters cytokine protein secretion, leading to heightened inflammation and increased numbers of immunosuppressive myeloid cells, thereby promoting cancer progression. Administering immunotherapy when these cells are most abundant significantly enhanced the efficacy of immune checkpoint blockades in solid tumors.

"As we enhance our understanding of the fundamental mechanism of circadian regulation of immunity, we will be able to harness the power of the body’s natural rhythms to fight cancer and develop more personalized and effective treatment strategies," said Bridget Fortin, lead author and UC Irvine doctoral student.

The study marks a significant advancement in defining circadian control over anti-tumor immunity. Future research will explore additional factors influencing time-of-day responses to checkpoint inhibitor therapy.

This work was supported by various institutions including the National Cancer Institute, the V Foundation, and Johnson & Johnson.

UC Irvine’s Brilliant Future campaign aims to raise awareness and support for UC Irvine through engaging alumni and garnering philanthropic investment for student success, health and wellness, research, among other areas.

Founded in 1965, UC Irvine is ranked among the nation’s top 10 public universities by U.S. News & World Report. It has produced five Nobel laureates and contributes significantly to both local and state economies.

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