March 17, 2026

6 min read

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The case for timing medical treatments to daily circadian rhythms

A growing field of research suggests that some medical treatments, such as cancer therapy or vaccines, might be more effective when given at certain times of the day

By Lauren J. Young edited by Tanya Lewis

MirageC/Getty Images

Could your body’s biological clock determine how receptive you’ll be to treatments and therapies? Some evidence suggests yes. A string of recent animal studies and early clinical trials have shown that certain medical interventions, from vaccines to immunotherapies, might be more effective when they are timed to a person’s circadian rhythm, the body’s internal clock that drives essential biological functions such as sleep, eating, metabolism—and immune activity. And scientists are trying to tap the interconnection between circadian rhythms and the immune system through an approach called chronotherapy.

“Anything you look at is probably oscillating to one degree or another in your body, and almost every drug you can think of probably would benefit from some time-of-day analysis,” says Zachary Buchwald, a radiation oncologist and physician-scientist at Emory University.

Buchwald is currently leading a trial on timed immunotherapy for people with skin cancer called the TIME trial. He and others are trying to understand if there’s solid biological evidence to make the case for personalizing therapies based on an individual’s unique circadian rhythm—or finding ways to alter their internal clock to ensure the treatment works effectively. Scientific American spoke with Buchwald about how circadian rhythms are linked to the immune system, what ongoing clinical trials are investigating and what potential limitations the field must consider if timed therapies become the norm.

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[An edited transcript of the interview follows.]

Tell me a bit about the history of chronotherapy.

A lot of this research was conducted by many other investigators who have been working on this for decades. The paper I came across that got me particularly interested in this topic was from a colleague of mine named Christoph Scheiermann in Geneva. He showed, in mice, that there is oscillation throughout the day in where immune cells are located. If you think of the immune parts of the body as different compartments—the blood and the lymph nodes—at one time of the day, there are more white blood cells, or T cells, in the lymph nodes. And then, 12 hours later, there are more immune cells in the blood. So it oscillates in a 24-hour circadian cycle.

This finding has been corroborated by others and shown, to a certain, extent in humans. To confirm it in humans, you would have to take out lymph nodes serially over a 24-hour cycle, which we’re not doing for obvious ethical reasons. But you can take blood many times over a 24-hour cycle, and there are changes that are associated with the time of day: data show that the frequencies of different T cell subsets in the blood oscillate throughout the 24-hour cycle.

How did you personally become interested investigating these timing-related effects for cancer therapies?

I had been studying lymph nodes fairly extensively in the lab, and we’ve known the lymph node that drains the tumor is very important for response to immunotherapy and cancer. And lymph nodes are super important for the response to anti-PD-1, which is a widely used antibody that helps stimulate the immune response to cancer.

In Scheiermann’s mouse study, he also showed that if you synchronize the timing of a vaccine with circadian-induced peak of T cells in the lymph node, that leads to a more robust immune response. I was fascinated by that.

Given those findings, I hypothesized that something similar might be happening with antibody administration for treating cancer. To test that idea, we did a very simple retrospective analysis asking the question: If patients get more of their antibody infusions at a specific time of day, do they live longer? We published that first study in the Lancet Oncology in 2021. It showed that if patients get more of their infusions very late in the day, they live a shorter period of time.

> “I would not be surprised if there are many other areas of research and contexts where circadian rhythm could have significant implications.”

—Zachary Buchwald, oncologist, Emory University

What is the basis of the TIME trial you’re currently running?

It is a phase 2 randomized study for patients with advanced melanoma who are getting an immunotherapy called ipi-nivo, or ipilimuma