How well a cancer treatment works may depend on the time of day you get it
By Brenda Goodman, CNN
(CNN) — Researchers recently tried an experiment: Gather people who had the same kind of lung cancer and put them on the same type of treatments to fire up their immune systems. The only difference was that half the group got their medications earlier in the day, before 3 p.m., and the other half got them later.
The surprise finding was that the time of day made a difference: Patients who got their first rounds of treatments in the morning had, on average, about five more months before their cancers grew and spread, a measure doctors call progression-free survival — and they lived almost a year longer than those who got their treatments later. They also had better odds of being alive at the end of the study, which has been running for more than two years.
Researchers have long studied the body’s clock, its circadian rhythm, which governs a host of biological functions including the release of hormones, when we feel hungry or tired, body temperature, blood sugar and blood pressure. There are dozens, if not hundreds, of smaller clocks under the control of this master clock at work in cells and tissues.
More recently, scientists who study these body clocks have discovered that the immune system seems to be exquisitely sensitive to timing.
Evidence is mounting that timing may influence how protective vaccines are and the odds of an adverse events after heart surgery. One study found that valve replacement surgery was less risky for patients when it was performed in the afternoon, for example.
The new study, led by researchers in China, was the first to test something that other groups had documented in observational studies. Previous research that looked back at when melanoma and kidney cancer patients received their treatments had reached strikingly similar conclusions: Cancer patients appeared to get far more benefit from immunotherapy drugs when they get them earlier in the day.
Although many experts are excited about the new findings, they’re approaching with caution.
The results are “exceptionally compelling,” said Dr. Zach Buchwald, an oncologist at Emory University’s Winship Cancer Institute who was not involved in the research. “If this were a new drug, they would be hailed far and wide as having discovered something revolutionary.”
But there are questions about why the time of day would be so impactful when immunotherapies are active in the body for weeks after they’re given through IV infusion. The study authors say it’s a valid question and one they can’t answer yet.
“This is possibly the most controversial finding in immune-oncology,” Dr. Paolo Tarantino, a breast medical oncologist at Dana-Farber Cancer Institute and Harvard Medical School in Boston, posted on X. “The effect size is hard to believe. Though [randomized-controlled trials] are hard NOT to believe. We need a coordinated effort … to investigate this.”
The study’s authors want that to happen, too.
“It’s really dramatic that we see this that strongly in patients,” said Dr. Christoph Scheiermann, a co-author of the new research, who studies the circadian rhythms of the immune system at the University of Geneva in Switzerland.
“And I agree … with everybody who questions this, that it needs to be replicated in other cohorts, on other continents.”
At least one such confirmatory study is already underway. Buchwald and his colleagues are in the process of enrolling patients in a similar randomized trial that will test the timing theory on immunotherapy for melanoma patients. The team aims to enroll 100 patients between Emory and Massachusetts General Hospital in Boston.
Testing timing in cancer treatment
The new study, published this week in the journal Nature Medicine, enrolled 210 patients who were diagnosed with non-small-cell lung cancers. The patients were evenly split into two groups and randomly assigned to get their first rounds of immunotherapy treatments either before or after 3 p.m.
The time cutoff was chosen because previous studies had suggested that the immune system may slow down for the day between 2 and 3 p.m.
After the researchers followed the patients for more than 28 months, the effects on cancer progression and survival were pronounced.
The patients in the early treatment group survived nearly a year longer, on average, than those who got those same medications after 3 p.m.
Getting those first rounds of treatment early in the day also nearly doubled the amount of time the drugs were able to keep the cancers from growing and spreading. Patients in the early treatment group had no cancer progression for an average of 11.3 months, compared with 5.7 months in the later treatment group.
At the end of the study, about 45% of the 105 patients who were randomly assigned to the early treatment group were still alive, compared with about 15% of the 105 who were assigned to the group treated later in the day. As of late January 2026, 75 patients in the study are still alive, the authors said, adding they hoped to publish an additional study at a later date on survival in the trial.
Blood tests of patients who received treatment earlier in the day also showed that they had more cancer cell-killing immune cells than those who got their treatment later.
Why treatment timing may matter
Long before trying this in humans, Scheiermann conducted carefully controlled experiments to understand the different clocks that govern parts of the immune system — in mice.
Mice and humans are not the same. But those preclinical studies uncovered how T cells, specialized white blood cells that are programmed to recognize and exterminate threats like cancer, are more active in the morning.
Scheiermann found that these specialized cells also cycle in and out of tumors throughout the day.
Cancer is clever, however, and knows how to switch off these powerful fighters. Cancer cells make a protein that effectively puts T cells to sleep and prevents them from attacking tumors.
“T cells in cancer become – there’s a term called exhausted,” Buchwald said. “They just don’t work as well. The cancer has evolved ways to suppress the immune response.”
Immunotherapy treatments called PD-1 inhibitors, the type of drugs used in the new study, block this interaction so T cells can still recognize and fight the cancer.
“The prevailing theory is that in morning times, there are more T cells physically in the tumor. And so if the drug shows up, then then there are more T cells there to react and start killing cancer cells,” Scheiermann said, adding that he’s doing further studies now to understand the biology of these effects in humans.
And although the timing of the first exposure to immunotherapy drugs seems to be very important, the timing of later rounds of the same drugs doesn’t seem to matter as much, Scheiermann said, for reasons that aren’t yet clear.
Your body’s exquisitely fine-tuned clock
“Every layer of the immune system seems to have a biological rhythm,” said Dr. Jeffrey Haspel, a pulmonologist at Washington University in St. Louis who studies circadian rhythms in critically ill people. His team found that CAR-T therapy – specially programmed T cells that fight blood cancers such as leukemia and lymphoma – also seems to work better and have fewer side effects when given in the morning.
“The very first encounter between the tumor and the drug and the T cell, that first-contact situation, may actually matter a lot to the long-term success,” said Haspel, who was not involved in the new research.
Other kinds of cancer drugs may be sensitive to timing, too. A 2021 study found that half of 126 of the anticancer drugs screened fought cancer more effectively at certain times of the day, said study author Dr. Amita Seghal, who directs the Chronobiology and Sleep Institute at the University of Pennsylvania’s Perelman School of Medicine. She was not involved in the new research but said it’s “exciting work.”
Haspel says he understands the caution around the study findings. Scheduling patient care is difficult, and doctors wouldn’t want to reorient the entire system unless there was a good reason to do it.
“If you’re going to reorganize the process of care, is the juice really worth the squeeze?” Haspel asked. “Is the amount of benefit that the patient could actually realize worth going through the trouble of actually scheduling people at particular times of day?
“What’s interesting is that these cancer immunotherapies seem to make the grade in terms of the size of the effect from morning scheduling.”
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