Asking about someone’s age is a well-known taboo. Unless, of course, you are asking a child. Then the topic of age is one that frequently brings joy and a sense of pride with each passing year. In addition to one’s chronological age, researchers are learning that understanding one’s “immunological age” is also highly relevant for children, especially those with cancer. As we age, some populations of immune cells change in abundance and these changes can be measured and used to infer one’s immunological age. This type of analysis is especially helpful for understanding the presence of premature immune aging in children. The most common form of cancer in children (<20 years old) is leukemia, a cancer of blood cells. Although survival rates are high for children after leukemia treatment, they are still susceptible to pathogens. To inform revaccination plans of these children and understand their comorbidity risk, it is critical to understand the immune state of these children. Dr. Madhav Dhodapkar, the Scientific Director of the Multiple Myeloma Program, and Dr. Kavita Dhodapkar, Professor in the Translational and Therapeutic Sciences Division at Fred Hutchinson Cancer Center, analyzed the T cell populations from children with and without leukemia to understand the immune state between these two groups. These analyses were also performed before and after successful treatment of leukemia. Their findings were published in npj Aging.
To understand how the T cell status of childhood leukemia survivors differed from healthy children of the same age, the researchers compared the abundance of T cell subtypes between leukemia survivors and age-matched healthy children. Key findings from this comparison were changes in T cell differentiation states. Specifically, childhood leukemia survivors had higher levels of T cell subsets with terminal differentiated states—indicative of replicative senescence or aging. The researchers also performed an analysis that separated T cells into clusters based on the presence or absence of specific T cell markers. This method included defined T cell profiles that are associated with immunological age that was developed to understand immune aging in children with Down syndrome. Following this prior study, the Dhodapkar lab defined “immunological age” by determining age-associated changes in T cell populations from about 100 healthy individuals with varied ages (across seven decades). Certain T cell subtypes were found to increase with increasing age while others decreased. This data set was used to interpolate age for the cohort of children with leukemia as compared to age-matched healthy children and included two datapoints from each leukemia patient for before and after successful leukemia treatment. What the researchers discovered next was very unexpected. “These studies led to the surprising finding that survivors of childhood cancer have advanced immune aging and that immune aging in survivors is already present at the time of their cancer diagnosis even prior to starting therapy,” stated Dr. Kavita Dhodapkar. “This is in contrast to the notion that immune changes in survivors largely reflects effects of cancer therapy.”
If treatment of leukemia is not a significant driver of immune aging, then how are changes to immune cell populations regulated? “Ongoing studies are addressing the mechanism of immune aging and how immune aging impacts observed risk of chronic morbidities in these survivors,” shared Dr. Kavita Dhodapkar. Therefore, future work from these scientists will shed light on drivers of immune aging and the risks of secondary illnesses for childhood leukemia survivors.
The spotlighted research was funded by the National Institutes of Health.
Fred Hutch/University of Washington/Seattle Children's Cancer Consortium members Drs. Kavita Dhodapkar and Madhav Dhodapkar contributed to this work.
Dhodapkar KM, Castellino S, Kapadia S, Azeem MI, Horvat A, Lawrence T, DeRyckere D, Dhodapkar MV. 2025. Immune-aging at diagnosis determines T-cell recovery in childhood leukemia survivors. npj Aging. 11(1):39.
Science spotlight writer Annabel Olson is a postdoctoral research fellow in the Nabet lab at Fred Hutchinson Cancer Center. Her research focuses on studying the mechanisms that drive cancer development for both genetic and virus-associated cancers. A key tool in her research is the use of targeted protein degradation to dissect dysregulated signaling pathways in cancer and to double as a relevant pre-clinical therapeutic platform.
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