Our body’s circadian clock affects everything from sleepiness to metabolism – and it might also influence how effective certain cancer treatments are, according to recent research.
Checkpoint inhibitors are immunotherapy drugs that block crucial proteins from binding to cancerous tumors, meaning the immune system’s T cells can more easily recognize and kill the cancer off. They are a good idea in theory, especially as the drugs are less toxic than chemotherapy, but scientists are trying to find ways to increase the impact of this approach in practice.
In the US, several checkpoint inhibitor therapies are currently approved for human use, but while these drugs can treat a wide variety of cancers, they only work for some patients. Perhaps a person’s circadian rhythm plays into that outcome.
Here, a team from the University of California, Irvine (UC Irvine) found that in mouse models of colorectal cancer, the 24-hour circadian clock cycle affected both the strength of the defenses put up by tumors, and the ability of checkpoint inhibitors to fight them. What’s more, when the circadian rhythm was disrupted in the mice, it reduced the immune system’s ability to tackle cancer. This, together with plenty of previous research, suggests both lifestyle changes as well as treatment times could be helpful in fighting cancer.
Understanding precisely how circadian disruption promotes disease progression could lead to behavior modification to reduce cancer risk, says Selma Masri, a biological chemist at UC Irvine.
The Relationship Between Circadian Rhythms and Colorectal Cancer
Immunosuppressive Cells and Circadian Rhythms
In colorectal cancer, cancer tumors produce what are known as immunosuppressive cells to try and disable the body’s immune system protections. The study’s first finding was that the abundance of these cells changes in time with circadian rhythms.
| Time of Day | Immunosuppressive Cell Levels |
|---|---|
| Morning | Low |
| Afternoon | Moderate |
| Evening | High |
This suggests that the effectiveness of checkpoint inhibitor treatments could vary depending on when they are administered. The researchers found that the checkpoint inhibitor treatments worked best when the immunosuppressive cell levels were at their peak in the evening.
- Immunosuppressive cells help the cancer tumor evade the body’s immune defenses.
- The levels of these cells fluctuate over the 24-hour circadian cycle.
- Checkpoint inhibitor treatments are most effective when immunosuppressive cell levels are highest.
Disrupting Circadian Rhythms Aids Cancer Progression
The second finding was that body clock disruption increased these immunosuppressive cells even further, helping the cancer to progress. This suggests that maintaining healthy circadian rhythms is important for supporting the immune system’s ability to fight cancer.
- Disruption of circadian rhythms leads to increased levels of immunosuppressive cells.
- Higher levels of immunosuppressive cells help the cancer tumor evade the immune system.
- Disrupting the body’s natural 24-hour clock can therefore promote cancer progression.
Optimizing Treatments Based on Circadian Rhythms
The third finding was that the checkpoint inhibitor treatments were found to work best when the immunosuppressive cell levels were at their peak. This indicates that timing cancer treatments to align with the body’s natural rhythms could improve their efficacy.
- Checkpoint inhibitor treatments are most effective when administered during times of peak immunosuppressive cell levels.
- Coordinating treatment schedules with the body’s circadian cycle could boost the impact of these therapies.
- More research is needed to confirm these mechanisms in human cancer patients.
The Importance of Circadian Rhythms for the Immune System
Circadian Regulation of Inflammation
We found that proper regulation of circadian rhythms is necessary to suppress inflammation and support peak immune function, says Masri. Inflammation is a key driver of many diseases, including cancer, and circadian disruption can lead to excessive inflammatory responses.
- Circadian rhythms help regulate inflammation levels in the body.
- Disruption of the body’s internal clock can promote excessive inflammation.
- Maintaining healthy circadian rhythms is important for proper immune function.
Link to Biological Aging and Alzheimer’s
Scientists are continuing to explore links between our body clocks and the functions of the immune system. The managing or optimizing of our circadian rhythms has recently been linked to biological aging and Alzheimer’s disease.
- Circadian rhythm disruption is associated with accelerated biological aging.
- Disrupted body clocks may also contribute to the development of Alzheimer’s disease.
- Understanding the relationship between circadian rhythms and the immune system could lead to new treatments for age-related diseases.
The Impact of Modern Lifestyles
We also know that modern day living, from shift work to electric lighting, is interfering with our circadian rhythms – and maybe not for the better, as far as our body’s natural defenses are concerned.
- Factors like shift work and exposure to artificial light at night can disrupt the body’s internal clock.
- This disruption of circadian rhythms may have negative consequences for immune function and disease risk.
- Developing strategies to maintain healthy circadian rhythms in modern lifestyles is an important area of research.
Harnessing Circadian Rhythms for Cancer Treatment
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, says Bridget Fortin, a biological chemistry doctoral student at UC Irvine.
Personalizing Cancer Treatments
By considering an individual’s circadian profile, it may be possible to time cancer treatments to better align with their body’s natural rhythms. This could lead to improved outcomes and reduced side effects.
- Personalized treatment schedules based on circadian rhythms could boost the effectiveness of cancer therapies.
- Considering a patient’s body clock may allow for more tailored and effective treatment approaches.
- Further research is needed to optimize circadian-based cancer treatment strategies.
Lifestyle Interventions for Cancer Prevention
In addition to personalized treatments, understanding the link between circadian disruption and cancer progression could inform lifestyle recommendations for cancer prevention.
- Maintaining healthy sleep patterns and light exposure may help reduce cancer risk.
- Behavior modification to support circadian rhythms could be a valuable cancer prevention strategy.
- Integrating circadian principles into cancer prevention programs is an emerging area of focus.
Combination Therapies Targeting Circadian Rhythms
The research also suggests that combination therapies targeting both the cancer and the patient’s circadian rhythms could be a promising approach.
- Combining cancer treatments with interventions to support healthy circadian rhythms may enhance therapeutic efficacy.
- Targeting both the tumor and the body’s internal clock could provide a more comprehensive cancer-fighting strategy.
- Further exploration of combination therapies that leverage circadian principles is warranted.
Conclusion
Our body’s internal clock plays a crucial role in regulating various physiological processes, including immune function. The growing evidence suggests that harnessing the power of circadian rhythms could lead to more effective cancer treatments and prevention strategies.
By understanding the intricate relationship between the body’s natural 24-hour cycle and the progression of cancer, scientists are uncovering new avenues for personalized and targeted therapeutic approaches. As we continue to explore the fundamental mechanisms underlying this connection, the potential to harness the body’s circadian rhythms for improved cancer outcomes becomes increasingly promising.
