Cancer Patients' Circadian Rhythms Could Be Used to Improve Their Immunotherapy

Immune checkpoint inhibitors are a form of immunotherapy that blocks checkpoint proteins from binding to tumor cells, which helps T cells recognize a tumor is a threat and more successfully kill cancer cells. New research finds that their effectiveness could be improved by using a patient’s natural circadian rhythm.

Research recently published in the journal Nature Immunology investigated how tailoring the time of a patient’s immunotherapy treatments to their body’s natural sleeping and waking cycle may help improve their immune system’s ability to fight back against cancer.

To test this, the research team – from University of California, Irvine – used a genetic model of colorectal cancer and a single-cell RNA sequencing technique. They focused on times of day at which there’s a larger number of immunosuppressive myeloid cells and when a certain type of T cell is being suppressed. They found that immunotherapy is best administered when these myeloid cells are most abundant, as it helps immune checkpoint inhibitors in the attack against tumors. The research suggests that this may be a good way to fine tune treatments.

Bridget Fortin, lead author and UC Irvine doctoral student in the Department of Biological Chemistry, says, “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.”

They also found that disrupting the internal clock in epithelial cells in the intestine impacts the secretion of cytokine protein, which leads to more inflammation, immunosuppressive myeloid cells, and cancer growth. The researchers say that may highlight another reason why consistent sleep patterns are important.

Selma Masri, study co-author and UC Irvine associate professor of biological chemistry, explains, “Disruption of the internal biological pacemaker is an inherent aspect of modern society that may contribute to the rising incidence of many cancer types. We found that proper regulation of circadian rhythms is necessary to suppress inflammation and support peak immune function. Understanding precisely how circadian disruption promotes disease progression could lead to behavior modification to reduce cancer risk.”

The team hopes further research investigates other factors that influence how certain times of the day can help with this type of immunotherapy.