Circadian rhythms could be used to improve the effectiveness of cancer immunotherapy

An interdisciplinary team of researchers from the University of California, Irvine has found that circadian rhythms, a biological regulator that controls the daily rhythms of physiological processes, including immune functions, can be used to improve the effectiveness of cancer immunotherapy using checkpoint inhibitors. These inhibitors block various proteins that prevent them from binding to tumor cells, allowing the immune system's T cells to destroy the tumor.

The study, published in Nature Immunology, deepens understanding of the complex relationships between circadian rhythms, immune regulation and tumor development, and shows that a therapeutic approach that optimizes the timing of administration drugs depending on individual circadian rhythms, opens up new opportunities for prevention and treatment.

"Disruption of the internal biological rhythm is an integral part of modern society and may contribute to the increase in the incidence of various types of cancer. We found that proper regulation of circadian rhythms is necessary to suppress inflammation and support maximum immune system function," said lead author of the study Selma Masri, Associate Professor of Biological Chemistry at the University of California, Irvine. "Understanding how disruption of circadian rhythms contributes to disease progression may lead to behavioral changes to reduce cancer risk."

The team used advanced single-core RNA sequencing techniques in a genetic model of colorectal cancer and identified circadian rhythm-dependent changes that control the number of myeloid cells that suppress T-cell activation. They found that disruption of the intrinsic biological rhythm in the epithelial cells lining the intestines alters cytokine secretion, leading to increased inflammation, increased numbers of immunosuppressive myeloid cells, and cancer progression.

These findings demonstrated that administering immunotherapy at times of day when the number of immunosuppressive myeloid cells is highest significantly increases the effectiveness of checkpoint blockade in treating solid tumors.

"As we deepen our understanding of the fundamental mechanism of circadian immune regulation, 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 lead study author Brigitte Fortin, a doctoral student in the department. In Biological Chemistry from the University of California at Irvine.

Although this study represents a significant step forward in defining the circadian control of antitumor immunity, the team believes that future research should focus on examining additional factors and cell types that influence response to checkpoint inhibitor therapy as a function of time of day. p>

The team also included graduate students and faculty from the University of California Irvine School of Medicine from the departments of biological chemistry, physiology and biophysics, surgery and medicine.