A study led by Professor Petter Brodin, a pediatrician and immunologist at the MRC Laboratory of Medical Sciences (LMS) and Imperial College London, analyzed 191 children aged 0 to 18, all diagnosed with various solid tumors at Stockholm’s Astrid Lindgren Children’s Hospital between 2018 and 2024. Researchers examined tumor samples to identify genetic mutations and took blood samples to see which immune cells and pathways became active in response to the cancer.
The first evidence of unique pediatric immune response
The findings reveal notable differences between how children’s and adults’ immune systems react to tumors. The pediatric cancers generally showed fewer mutations and were less inflammatory, suggesting that they can appear “less foreign” to a child’s immune system. The study also found that immune responses varied by tumor type.
“The activation of the immune system is crucial to our ability to fight cancer, but differs between children and adults,” says Petter, Head of the Systems Immunology Group at the LMS and Professor at Karolinska Institutet, interviewed in Imperial. “If we’re to properly treat childhood cancer, we need to find out how the child’s immune system is activated and regulated in children with cancer and what factors affect their immune responses.”
“Precision medicine in cancer has mostly focused on the tumor properties,” Petter adds. “By characterizing the immune system, we’re introducing an entirely new dimension that will be instrumental in shaping the future of childhood cancer therapy.”
Why immunotherapy may not suit children — yet
Because children’s cancers appear less inflammatory, they often fail to spark a robust immune reaction. This could explain why pediatric patients do not typically benefit from certain immunotherapies, such as checkpoint inhibitors.
“This requires the immune cells to be activated against the tumor,” Petter says. “We show that the child’s immune cells are often initially not activated against the tumor, which means that checkpoint inhibitors won’t work. Children likely need different types of immunotherapies that are more focused on triggering the immune cells to attack the tumor cells from scratch.”
Tracking immune responses over time gave the team additional insight. By measuring changes in killer T cells, the researchers could potentially gauge the effectiveness of treatment and customize it in real-time.
“This is something that we could make clinical use of today to judge the therapeutic effect and adjust the treatment to every individual patient,” Petter continues. “We’ll now be testing this on a larger scale as we believe that it can be a useful complement to the genetic analyses of tumors that are already being done in routine care.”
Path forward for pediatric cancer treatment
Launched in 2018, the project lays the groundwork for developing immunotherapies that better match children’s unique immune profiles. Petter’s Systems Immunology Group at the LMS aims to refine strategies for stimulating a stronger anti-tumor response in younger patients based on factors like age and tumor biology. Additional research will be critical for translating these findings into widely available pediatric therapies.
Petter and co-lead investigator Dr. Linda Ljungblad of Karolinska Institutet conducted the study in partnership with the Astrid Lindgren Children’s Hospital pediatric oncology clinic at Karolinska University Hospital. Funding was provided by the Swedish Cancer Society, the Swedish Childhood Cancer Foundation, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and Karolinska Institutet.
Reference: Chen et al., Systems-level immunomonitoring in children with solid tumors to enable precision medicine, Cell, 20 January 2025, doi: 10.1016/j.cell.2024.12.014.
