Immunotherapy has the best anti-cancer time, and it is effective to choose the right time. (Kateryna Kon/Shutterstock)
Although cancer cells can appear anywhere in our body at any time, fortunately, they almost alwaysRecognized and eliminated by the immune system.Immunotherapy, a type of cancer treatment, helps a person’s immune systemfight cancer。
Scientists have discovered that the effect of immunotherapy is affected by biological rhythms – if it is used at the right time, it can achieve better anti-cancer effects.
The immune system has different effects on clearing cancer cells at different times
The biological clock in our body, according to the laws of nature, runs 24 hours a day and supports countless physiological processes. for example,HepatocyteDigestive enzymes are produced before breakfast so that they can be provided while digesting breakfast.
immune system alsoaffected by the biological clockits ability to recognize and eliminate cancer cells is different at different times.
In December 2022, scientists from the University of Geneva and the Ludwig-Maximilians University of Munich published a paper in the journal NatureResearchexplained a highly operational method that can improve the effectiveness of cancer treatment: choosing the right time to use immunotherapy to fight cancer may achieve the effect of “doing twice the result with half the effort”.
In other words, simply changing the timing of treatment, cangreatly enhances its effectiveness.But conversely, ignoring this may lead toMissed opportunity to fight cancer。
The researchers first injected cancer cells into healthy mice at different times, and found that the timing of the injections affected the development of the cancer: If the mice were injected with cancer cells during the resting period, the tumors grew slower, and if the mice were injected during the active period, the tumors grew slower. cancer cells, the tumor grows faster.
Strangely, this difference was not seen in the immunocompromised mice, prompting the researchers to study the role of immune cells in more detail.
They observed that slower-growing tumors contained more of a type of immune cell called killer T cells, which can kill cancer cells, than faster-growing tumors.
Behind the killer T cells, there is also a key immune cell – dendritic cells (dendritic cells). They ingest cancer cell components to deliver and activate killer T cells.
To put it vividly, in this process, the role of dendritic cells is like a sentinel. He discovered the criminal (cancer cell) and took a photo, and then sent the photo of the criminal to the heavily armed special forces (killer T cells). After taking the photo of the criminal, the special forces turned into a combat state to accurately identify the criminal and eliminate him decisively.
During the rest period, immune cells are more alert and effective in fighting cancer
The study also reported that compared with mice injected with cancer cells during the active period, mice injected with cancer cells during the rest period not only had more dendritic cells in the body, but these cells were also more “vigilant” – They express more proteins that are effective in activating cytotoxic T cells.
This means that not only are the sentinel dendritic cells produced in greater numbers during the organism’s rest period, but they are also more active in promoting the switch from standby to fighting state of special forces killer T cells.
However, when mice were injected with cancer cells after disrupting the dendritic cell clock, tumor growth was no longer affected by the time of injection. The researchers said that this shows that the initiation of the anti-cancer effect of dendritic cells is regulated by the biological clock.
At present, anti-cancer vaccines are also regarded as a type of immunotherapy, which usually contain ingredients specific to cancer cells, designed to stimulate immune cells to attack malignant tissues. Therefore, the researchers hypothesized that administering anticancer vaccines at specific times of the day could improve the effectiveness of the treatment.
The effective anti-cancer time of the human body
It is worth emphasizing that this study used mice for animal experiments, and mice are nocturnal animals whose biological rhythm is just opposite to that of humans.
“The point is that the time of day for any other treatment that involves activation of the immune system may be important,” the researchers said in the report.
The researchers also analyzed a 2005 human study published in the Journal of Clinical Investigation. The study gave skin cancer patients a form of immunotherapy — injections of cancer-fighting vaccines. The data showed that the effect of the morning treatment was better than that of the afternoon — an increase in specific T cells in the patient’s blood.
In fact, many studies have found that immunotherapy works better during the day.
The most common type of immunotherapy is immune checkpoint inhibitors.
In November 2021, researchers at the Winship Cancer Institute at Emory University in Georgia published a study in The Lancet.Research. They administered immune checkpoint inhibitor injections to 299 patients with advanced melanoma. The researchers found that if the injection was given at night, the patient’s adaptive immune response was not as strong as when the injection was given during the day.
Therefore, they suggested that patients with advanced melanoma should be infused with immune checkpoint inhibitors, preferably before three o’clock in the afternoon.
There are also studies with slightly different findings.
In a 2020 publishedResearchAmong them, 30 patients with metastatic renal cell carcinoma were divided into three groups and received interleukin-2 at different time periods (5:00-13:00, 13:00-21:00 and 21:00-5:00). treat.
Injection of interleukin 2 is a non-specific immunotherapy designed to enhance the immune response in cancer patients.
Results showed that patients treated in the morning and evening had a longer median overall survival compared with those treated in the afternoon and evening, but the study showed that the difference was not significant.
Treatment in the morning may have fewer side effects
In another study of 95 patients with metastatic non-small cell lung cancerexperimentIn the study, with 12:55 as the dividing line, patients were divided into “morning group” and “afternoon group” and were injected with immune checkpoint inhibitors.
The results showed that patients in the morning group reported relatively lower rates of fatigue, anorexia, and myalgia.
Notably, the median cancer progression-free survival was 11 months in the morning group compared with 3 months in the afternoon group. In addition, the median overall survival was 34 months in the morning group compared with 10 months in the afternoon group.
From this, the researchers concluded that morning dosing was not only less toxic than afternoon dosing, but also four times as effective as afternoon dosing.
Author of the study published in the originally mentioned Nature journal, Christoph Scheiermann, Professor, Department of Pathology and Immunology, University of Geneva Faculty of Medicine, Geneva Center for Inflammation Research and Center for Translational Research in Oncology and Hematologythink“immune activation fluctuates throughout the day and peaks in the late phase of the quiescent phase.”
For the study at the University of Geneva and the Ludwig-Maximilians-Universität Munich, researchers at the Charité – Universitätsmedizin Berlin, Institute of Medical Immunologyexpresscleverly choosing the timing of an intervention, “such as when treatment is most effective and has the fewest side effects”, may improve the efficacy and safety of the therapy, while also saying “we should not miss this opportunity”.
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Responsible editor: Li Qingfeng◇