Could the Right Time of Day Boost Cancer Treatment Response in Dogs??

Today's cancer treatments for dogs have a long way to go, especially in terms of effectiveness.

What if not just what treatment your dog receives, but when it’s given, could influence how well it works?

Scientists are beginning to understand how timing can significantly impact the effectiveness of treatments.

The Science Behind It

Every cell in the body, including immune cells and tumor cells, contains molecular clocks.

Expression of genes and proteins operates on a ~24-hour circadian rhythm, regulating processes such as cell division, metabolism, and DNA repair. Importantly, they also influence how immune cells recognize and attack cancer.

A recent 2024 study in Cell found that in mice, the number of cancer-killing CD8⁺ T cells inside tumors oscillated during the day. When mice received immunotherapy treatment in the evening (their active period), the tumors shrank more compared to morning treatment.

In people, similar daily fluctuations in immune activity have been observed in tumor biopsies; the tumor microenvironment is dynamic, not static.

Mice are nocturnal, and their “evening” corresponds to humans’ and dogs’ daytime.

Could selecting the right time of day help more canine patients respond to cancer treatment?

Human Studies on Immunotherapy Timing

Immune checkpoint inhibitors (ICIs) are a form of cancer treatment that works by activating the immune response.  ICIs are among the most important cancer treatments available for human cancer patients - and they are also becoming available for dogs.

The FDA has approved multiple types of ICIs for different cancer types for people, and one important thing to know is that they do not work for all patients.  Only a subset of patients responds and experiences long-term remissions.  This is also true for canine patients.

Learn About ICI

Could choosing the treatment times make a difference in how  ICI and other immunotherapy treatments work?

In a 2023 study, researchers found that patients with metastatic melanoma treated earlier in the day had longer median survival times than those treated later in the day.

Their paper, “Immunotherapy Around the Clock: Impact of Infusion Timing on Stage IV Melanoma

Outcomes” , analyzed data from 73 patients who received a total of 1019 ICI immunotherapy infusions. 

The infusion times were split into two groups:  morning AM group (8am - 2pm) and afternoon PM group (2pm - 8pm).  The AM group included patients who received less than 75% of the infusions after 2 pm, and the PM group included all the patients who received at least 75% of the infusions after 2 pm. 

Overall survival was strikingly higher in the morning group (median of 38.1 months) compared to the afternoon group (14.2 months). The Kaplan-Meier survival curve below contrasts the two groups (AM group, yellow dotted line; PM group, solid blue line)

Overall survival probability for patients in AM group (dotted yellow) was higher than for the PM group (solid blue)

When researchers divided the patients by age (65 and older), the benefits of morning infusions could also be observed. What's also interesting is that, while younger patients generally survived longer than older patients, the older patients receiving AM infusions did better than the younger patients receiving PM infusions.

Overall survival comparing patients in the AM and PM groups, in two age groups.

In a 2024 Japanese study with lung cancer patients,  researchers also observed a lower response rate for patients receiving most of the infusions after 3pm.

Progression-free survival comparing patients that received less than 20% of ICI infusions after 3 pm (blue) compared to those patients who received more than 20% after 3 pm (red)

In yet another 2025 study involving 349 patients with lung cancer, researchers found that those who received more than 50% of ICI infusions in the afternoon (after 2:30 pm) had shorter survival times.  

There have also been reviews and meta-analysis articles.

A 2024 article in the British Journal of Cancer summarized 18 retrospective studies covering ~3,250 patients across nine countries and multiple tumor types.  Earlier in the day, ICI timing had better progression-free survival and overall survival.  

Graphical summary of progression-free survival and overall survival from analyzing time-of-day administration of ICIs

A 2025 article provides a summary of various cancer type studies showing time-of-day boundaries chosen by the different studies. The time windows on either side of the boundary are shaded by improved (green) or worse (orange) outcomes.  Gray and hatched patterns indicate no difference or mixed results.  

As shown below, most studies indicate that treatments administered earlier in the day yield improved outcomes.

Graphical summary of efficacy outcomes from analyzing time-of-day administration of ICIs

Currently published human data are all based on retrospective studies. However, they associate earlier ICI delivery with a better response rate and survival.  Newer prospective studies are now underway.  

While canine ICI treatments (e.g., Gilvetmab) are now available and being evaluated, there have been no published data on the time-of-day dependence of efficacy.  

Based on human and mouse data, should vets be administering ICI immunotherapy treatments earlier in the day, avoiding late afternoon infusions?

Timing and Vaccines

Cancer immunotherapy doesn’t only include ICIs. It also includes cancer vaccines, which train the immune system to recognize tumor antigens. For dogs, several therapeutic vaccines are already in use or in clinical trials, including:

• Oncept (DNA vaccine for oral melanoma)

• EGFR/HER2 peptide vaccine (Yale/Therajan trial)

• Tumor lysate vaccines such as those from Elias Animal Health, Ardent, and Torigen

  
  

While there are no published studies yet on time-of-day effects in cancer vaccines, research on infectious disease vaccines offers compelling clues.

• In a Lancet study (2016), older adults vaccinated against influenza in the morning (9–11 a.m.) produced higher antibody levels than those vaccinated in the afternoon.

• Several COVID-19 vaccine studies have found stronger antibody responses after vaccination in the morning.

  
  

Because the immune system’s “readiness” oscillates through the day, vaccine efficacy may vary depending on when it’s administered, a finding likely relevant for cancer vaccines as well.

Implications for Canine Cancer Treatments

For canine patients, the timing question remains unexplored, but it’s highly relevant.

Therapies like Gilvetmab (PD-1 immune checkpoint inhibitor for canine patients), therapeutic cancer vaccines, and adoptive cell therapies all depend on immune activation. Given what we know from humans and mice, it’s biologically plausible that morning administration could produce stronger immune responses and more durable effects.

Until veterinary studies are conducted, treatment timing should strike a balance between scientific plausibility and practicality.

Take-Home Message

• The immune system follows a daily circadian rhythm that shapes how it responds to cancer therapies.

• Human and mouse studies show that time of day can impact the efficacy of immunotherapy and vaccines.

• While no canine-specific data exist yet, early-day treatment might hold advantages.

• If your dog is receiving immunotherapy (including cancer vaccine treatment), it's worth asking your veterinarian whether an earlier treatment time might be beneficial.

  
  

Get Your Free Immunotherapy Guide

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Check out other articles and videos

• 8 Things Pet Parents Should Know About Elias Immunotherapy for Canine Cancer

  
  

  

• A New Immunotherapy Trial for Dogs with Lung Metastases: The CAALM Study

• Remarkable 12 month survival-rate with Elias Immunotherapy

Questions? Email us at info@ccralliance, and we'll get back to you as soon as we can!

Canine Cancer Alliance is a non-profit organization supporting research for canine cancer cures.

All information on the Canine Cancer Alliance website is for educational purposes only. It is not intended to be a substitute for professional veterinary advice.

Always seek guidance from your veterinarian with any questions regarding your pet’s health and medical condition.