Animal Models for Cancer Immunotherapy Research Should Reflect Older and Obese Patient Populations
More accurate modeling of cancer, which affects the elderly more than younger populations, could speed breakthroughs in research. Therefore, research on immunotherapy for cancer should include obese and older mice.1
"Because most cancer patients are older than 60 years of age, it can be convincingly argued that all preclinical studies testing novel immunotherapies or new combinations should include older mice. Yet this approach is rarely taken," said corresponding author Ryan Teague, PhD, associate professor of molecular microbiology and immunology at Saint Louis University, St Louis, Missouri.
Although the advent of immunotherapy has the potential to save lives, the best animal models are not being used to predict the efficacy of immunotherapy in diverse populations. The immune system becomes less responsive with age, as is observed with T cells, which decrease in number as a person ages. This decrease results in a less effective ability to attack cancerous cells as in younger people.
Nonetheless, young, healthy mice are generally used in cancer immunotherapy research.
"Despite decades of research into the gradual deterioration of the immune system during aging, this still represents fertile territory for clinically significant discoveries. Direct comparisons of old and young mice in translational preclinical investigation is crucial moving forward," Teague explained.
"Older mice represent imperfect but valuable models for human immune aging and may prove far more accurate than young mice in predicting the efficacy and potential toxicity of novel cancer immunotherapies in this major patient demographic."
This review, published in Trends in Immunology, encourages the use of diversity in mice, including old, young, obese, lean, and those with different microbiota, to most accurately reflect the diversity in people who develop cancer. Laboratory mice are elderly at age 16 to 24 months.
Age is not the only factor affecting responses to immunotherapy. Body weight and gut microbes also affect the body's immune system and, therefore, the response to immunotherapy.
"What determines the success of immunotherapy among diverse patient populations? Insight has come from recent mouse studies revealing that age, obesity, and microbiota profoundly influence both natural immunity to cancer and the ability to effectively respond to immunotherapy,” said Teague.
“This area of investigation is in its infancy, but results are sufficiently compelling to force new thinking into how human cancer immunotherapy is modeled in mice."
1. Klevorn LE, Teague RM. Adapting cancer immunotherapy models for the real world [published June 2016]. Trends Immunol. doi:10.1016/j.it.2016.03.010.