Sub-Journal of The Lancet: Is immunotherapy administered during the day or at night?

*Only for medical professionals to read for reference! Come and find out! In traditional medicine, the twelve hours of the day correspond to different viscera, and many medicines must be taken at specific hours to get the best effect
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Whether these claims in traditional medicine have a scientific basis is aside for the time being, but it is true that taking medicines at different times of the day causes differences in therapeutic effects
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For example, antihypertensive drugs, taking it before going to bed at night can reduce the risk of cardiovascular death by 56% compared with taking it after waking up in the morning [1]
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For example, when temozolomide is used to treat glioblastoma, the survival period of patients who take the medicine in the morning is 3 to 4 months longer than that of the medicine at night [2]
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This phenomenon also exists in tumor immunotherapy
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Recently, The Lancet Oncology published a study that the time for melanoma patients to receive immunotherapy has a certain impact on the survival of patients, and PD-1 inhibitors may be best injected before 4:30 in the afternoon [3]
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Patients with more than 20% of the doses injected after 4:30 in the afternoon have more than doubled the risk of death compared to patients with more than 80% of the doses injected before 4:30
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Screenshot of the journal's official website.
This is the first study on circadian rhythms in immunotherapy
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The sunrise takes place at sunset.
Since ancient times, human beings have lived day after day according to this circadian rhythm, and many physiological activities of the human body are also affected by the circadian rhythm, including the immune system
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The distribution of immune cells in the blood, lymph and tissues will change periodically with the circadian rhythm [4]
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Studies have also found that the effect of vaccination during the day is better than vaccination at night, and it can induce stronger immunity [5]
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How does periodic changes in the immune system affect tumor immunotherapy? SBuchwald et al
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conducted a study on melanoma patients receiving immunotherapy .

The study included 299 adult patients with stage IV melanoma who had received at least 4 doses of immunotherapy
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Of these patients, 34% were women, with a median age of 61 years old.
The immunotherapy drugs used included K drug (pembrolizumab), O drug (nivolumab), and Y drug (ipilimumab) And double immunotherapy
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With 4:30 pm as the boundary, the researchers divided these patients into two groups
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In one group, more than 20% of the treatment doses were injected after 4:30, a total of 74 people; in the other group, more than 80% of the doses were injected before 4:30, a total of 225 people
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In the two groups of patients, the researchers selected 73 patients with similar basic characteristics for analysis
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▎Analysis results show that the overall survival of patients with more than 20% of the doses injected after 4:30 is significantly worse, the median overall survival is 4.
8 years, and more than 80% of the doses are injected before 4:30.
The overall survival period was not reached at the time of the data cut-off
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More than 20% of the doses were injected after 4:30, which increased the patient’s risk of death by 1.
04 times, and the 5-year survival rate was also reduced from 68% to 49%
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Patients with more than 80% doses injected before 4:30 in the afternoon have a longer overall survival time.
Considering that the three immunotherapy drugs have a biological half-life of 2 to 3.
5 weeks, it seems strange that the injection time will have such a big impact on the efficacy.

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Researchers believe this may be related to the initial tissue distribution after the injection of immunotherapy drugs
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Preclinical studies have shown that the concentration of drug K in tumor-draining lymph nodes and other lymphoid organs reaches a peak half an hour after injection, and is largely cleared after 12 hours [6], and tumor-draining lymph nodes are the most important site for enhancing anti-cancer immunity.

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Injecting immunotherapy drugs at different times may mainly affect the peak time of drug concentration in the lymphatic organs, which has an impact on the efficacy
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Although the timing of immunotherapy needs to be further studied on a larger scale, especially for people of different geographical locations and latitudes, there may be some differences in circadian rhythms, but researchers still suggest that in the immunotherapy of advanced melanoma, Consider injecting the drug before 3 pm
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Morning vaccination enhances antibody responseover afternoon vaccination:a cluster-randomised trial[J].
Vaccine,2016,34(24):2679-2685.
[6].
England CG,Ehlerding EB,Hernandez R,et al.
Preclinical pharmacokinetics andbiodistribution studies of 89Zr-labeled pembrolizumab[J].
Journal of NuclearMedicine,2017,58(1):162-168.
Source of this article: Dongdong Cancer Friends Circle Author of this article: Responsible Editor of the Department of Medicine of Dongdong: Sweet Author Recruiting Part-time Job in Oncology Channel of Medical Circle The author! If you are a [medical student] who [love to write], if you believe in [the value of dissemination of medical knowledge], please contact us~ Requirements: 1.
Bachelor degree or above in medicine (undergraduate degree must be a senior year or above); 2 , Have time, have interest, and have the pursuit of words; 3.
Be competent in English translation! Come and contact us~WeChat: result_crazy (it is better to attach the work, time is preferred~) *The medical community strives for the accuracy and reliability of the published content when it is approved, but it does not know the timeliness of the published content and the citations Make any promises and guarantees for the accuracy and completeness of the information (if any), and assume no responsibility for the outdated content and the possible inaccuracy or incompleteness of the cited information.
Source of this article: Dongdong Cancer Friends Circle Author of this article: Responsible Editor of Dongdong Medical Department: Sweet Author Recruitment Medical Tumor Channel Recruiting Part-time Authors! If you are a [medical student] who [love to write], if you believe in [the value of dissemination of medical knowledge], please contact us~ Requirements: 1.
Bachelor degree or above in medical major (Bachelor degree must be a senior year or above); 2 , Have time, interest, and pursuit of words; 3.
Be competent in English translation! Come and contact us~WeChat: result_crazy (it is better to attach the work, time is preferred~) *The medical community strives for the accuracy and reliability of the published content when it is approved, but it does not know the timeliness of the published content and the citations Make any promises and guarantees for the accuracy and completeness of the information (if any), and assume no responsibility for the outdated content and the possible inaccuracy or incompleteness of the cited information.
Source of this article: Dongdong Cancer Friends Circle Author of this article: Responsible Editor of Dongdong Medical Department: Sweet Author Recruitment Medical Oncology Channel Recruiting Part-time Authors! If you are a [medical student] who [love to write], if you believe in [the value of dissemination of medical knowledge], please contact us~ Requirements: 1.
Bachelor degree or above in medicine (undergraduate degree must be a senior year or above); 2 , Have time, have interest, and have the pursuit of words; 3.
Be competent in English translation! Come and contact us~WeChat: result_crazy (it is better to attach the work, time is preferred~) *The medical community strives for the accuracy and reliability of the published content when it is approved, but it does not know the timeliness of the published content and the citations Make any promises and guarantees for the accuracy and completeness of the information (if any), and assume no responsibility for the outdated content and the possible inaccuracy or incompleteness of the cited information.

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Relevant parties are requested to check separately when adopting or using this as a basis for decision-making
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