New research shows how children’s immune systems react differently to cancer than adult immune systems, and that their immune responses depend on the kind of tumour they have. The study shows that children's cancers are less likely to stimulate anti-tumour immune responses which are commonly seen in adult cancers and paves the way for new tailored treatments. The work was led by Professor Petter Brodin, paediatrician and immunologist at the MRC Laboratory of Medical Sciences (LMS) and Imperial College London.
By Emily Armstrong
January 20, 2025
Time to read: 4 minutes
The study, published today in the journal Cell, involved 191 children between the ages of 0 to 18 who were diagnosed with different types of solid tumours at the Astrid Lindgren Children’s Hospital in Stockholm Sweden between 2018 and 2024. The researchers analysed tumour tissue to determine what genetic mutations had occurred in them, and examined blood samples to ascertain which cells and pathways of the children’s immune system were activated in response to the cancer.
Difference between children and adults
The results show for the first time that the immune system of children reacts very differently in response to a tumour, to the immune system of adults. They also showed that the immune responses differed significantly depending on the kind of tumour they had.
“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. “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 tumour properties,” explains Petter. “By characterising the immune system, we’re introducing an entirely new dimension that will be instrumental in shaping the future of childhood cancer therapy.”
Children’s tumours are less inflammatory
“What we can see is that children’s tumours are generally less inflammatory and have fewer mutations, which means that they likely appear less foreign to the immune system and that the immune system therefore doesn’t attack the tumours as forcefully,” says Petter. “Having said this, there are large individual variations, which underlines the importance of precision medicine, which is to say the adapting of treatment to individual patients. Our study shows how this can be done in practice.”
Immunotherapy not suited to children
The results might explain why children do not benefit from immunotherapeutic treatments such as checkpoint inhibitors, a type of biological therapy that makes immune cells more effective against the tumour by blocking the proteins that disengage them.
“This requires the immune cells to be activated against the tumour,” says Petter. “We show that the child’s immune cells are often initially not activated against the tumour, 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 tumour cells from scratch.”
Tracking the child’s immune response
Having tracked the immune response over time and during treatment in some of the children, the researchers were able to measure changes in the population of killer T cells (i.e. the cells whose job it is to kill the tumour).
“This is something that we could make clinical use of today to judge the therapeutic effect and adjust the treatment to every individual patient,” he 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 tumours that are already being done in routine care.”
The future of personalised immunotherapies
This work, which began in 2018, lays the foundations for future immunotherapies targeted to the unique immune systems of children. At the LMS, Petter now leads the Systems Immunology Group, who are working on developing treatments that can boost the initiation of the immune response in children according to their age and tumour type.
Petter’s team focuses on understanding how certain factors and environmental exposures shape the immune system early in life. This is closely aligned with the overarching research strategy of the LMS to discover the mechanisms that underpin human health and disease, and how they are influenced by age, sex and environmental exposures.
Excitingly, the team is currently in discussion with life sciences companies in the UK that focus on translating early research into treatments to continue this work, which could one day transform outcomes for children with cancer.
Petter led the study with Linda Ljungblad, oncology resident and researcher at Karolinska Institutet. The study was conducted in close collaboration with the Astrid Lindgren Children’s Hospital paediatric oncology clinic at Karolinska University Hospital. It was funded by the Swedish Cancer Society, the Swedish Childhood Cancer Foundation, the Swedish Research Council, the Knut and Alice Wallenberg Foundation and Karolinska Institutet.
Publication: Chen et al., Systems-level immunomonitoring in children with solid tumors to enable precision medicine, Cell, online 20 January 2025, doi: 10.1016/j.cell.2024.12.014.
https://doi.org/10.1016/j.cell.2024.12.014
The original press release written by Karolinska Institutet: https://news.ki.se/new-study-paves-way-for-immunotherapies-tailored-for-childhood-cancers