Researchers have discovered how children’s immune systems respond to various cancers based on their age. This investigation indicates notable differences between the immune reactions of children and adults, offering the possibility for new, customized therapies for young cancer patients.
A team from Karolinska Institutet and the Astrid Lindgren Children’s Hospital in Sweden has found that children’s immune systems react differently to various cancers as they grow. The findings, published in the journal Cell, highlight substantial discrepancies in immune responses between children and adults, which could pave the way for innovative, personalized treatments for childhood cancer.
“Activating the immune system is essential in combatting cancer, yet this activation varies between children and adults,” explains Petter Brodin, a professor of pediatric immunology at Karolinska Institutet and a pediatrician at Astrid Lindgren Children’s Hospital, part of Karolinska University Hospital. “To effectively address childhood cancer, we must understand how a child’s immune system is activated and regulated when faced with cancer, as well as the factors that influence these immune responses.”
Introducing a New Aspect of Precision Medicine
The research involved 191 children, aged 0 to 18, diagnosed with various solid tumors at Astrid Lindgren Children’s Hospital from 2018 to 2024. The team examined tumor tissues and blood samples to identify genetic mutations within the tumors and to determine the active and inactive genes in the immune system.
“While precision medicine in cancer has largely concentrated on tumor characteristics,” says Professor Brodin, “our focus on the immune system introduces a fundamentally new aspect that will be critical for the future treatment of childhood cancer.”
Contrasting Responses Between Children and Adults
The findings reveal that the immune responses of children and adults to cancer differ significantly, and various tumors can activate immune responses to different extents.
“Our observations indicate that children’s tumors typically exhibit lower inflammation and fewer mutations, suggesting they may seem less foreign to the immune system, which results in a weaker immune response against the tumors,” notes Professor Brodin. “Nonetheless, there are significant individual differences, emphasizing the need for precision medicine, which implies customizing treatment for each patient. Our research illustrates how this can be implemented in practice.”
Challenges with Immunotherapy for Children
The findings could clarify why children often do not respond well to immunotherapy treatments like checkpoint inhibitors, which enhance immune cell efficacy against tumors by obstructing proteins that deactivate them.
“This approach necessitates that immune cells are activated against the tumor,” states Professor Brodin. “Our study indicates that children’s immune cells are frequently not primed to recognize the tumor from the outset, making checkpoint inhibitors ineffective. Children likely require alternative types of immunotherapies aimed at stimulating immune cells to first target tumor cells.”
Monitoring a Child’s Immune Response
By tracking immune responses over time and during treatment for some children, the researchers measured changes in the population of killer T cells, which are responsible for eliminating tumors.
“This information could be clinically utilized now to assess treatment effectiveness and tailor therapies for each individual patient,” Brodin adds. “We plan to expand this testing, as we believe it can effectively complement existing genetic analyses of tumors within routine healthcare.”
The study was spearheaded by Professor Brodin in collaboration with Linda Ljungblad, an oncology resident and researcher at Karolinska Institutet, and was conducted in strong partnership with the pediatric oncology clinic at Astrid Lindgren Children’s Hospital. Financial support came from the Swedish Cancer Society, the Swedish Childhood Cancer Foundation, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and Karolinska Institutet. Additionally, Petter Brodin and two other authors are founding members of Cytodelics AB, and Brodin is also on the executive board of Kancera AB and serves as a scientific advisor to several technology and health companies.
