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New Research Explains Why Immunotherapy Is Less Effective in Children With Cancer
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Key Takeaways
- Children's tumors often evade immune detection, leading to less effective immunotherapy outcomes compared to adults.
- Lower mutational burdens in children contribute to weaker immune responses to cancer immunotherapies.
Children and adults with cancer have differing immune system responses, mutational burdens, and tissue microenvironments.
Children’s immune systems respond to cancer immunotherapy differently from adults, according to a study from Karolinska Institutet. The researchers found that tumors in children with cancer often evade immune detection, suggesting why many existing immunotherapies fail in children. These findings could advance pediatric cancer treatment and introduce precision medicine tailored to the unique immune landscapes of young patients.
Adult holding hand of child with cancer | Image Credit: © pingpao - stock.adobe.com
Cancer is the leading cause of disease-related mortality in children and an estimated 15,780 children are diagnosed with cancer every year in the United States. Advancements in treatments greatly improved overall 5-year survival rates to almost 80%. However, many patients experience worse disease and poorer outcomes, namely those with solid tumors. Survival is dependent on surgery, cytostatic drugs, and radiation but these often yield late effects, such as heart damage, caused by aggressive treatment regimens.1,2
Immunotherapies, such as checkpoint inhibitors, have been revolutionary in the treatment landscape of various cancers, but few children benefit from these therapies and known markers of effective response are lacking. According to the researchers, differences in anti-tumor immune responses between adults and children is a significant factor driving poor immunotherapy responses in children.1
“The activation of the immune system is crucial to our ability to fight cancer, but differs between children and adults,” Petter Brodin, MD, PhD, professor of pediatric immunology at the department of women’s and children’s health at the Karolinska Institutet, and pediatrician at the Astrid Lindgren Children’s Hospital, part of Karolinska University Hospital, said in a press release. “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.”3
Compared with children, adults have higher mutational burdens, which suggests why they have superior responses to immunotherapies. Children have lower mutational burdens and aggressive treatment regimens are associated with increases in the mutational load in therapy-resistant or relapsing tumors. Additionally, adults’ immune systems are fully developed unlike children who experience developmental changes in composition and function of the immune system.1,3
To determine the factors influencing immune response in children, the researchers performed a systems-level analysis of immune responses in 191 children (94 females and 97 males) with diverse solid tumors within a population-based cohort. According to the findings, age and tumor type shape immune responses, as well as differences in tissue microenvironment, differences in embryonic origin, and proliferation rates. The results show that the immune system of children does not react the same as adults and different tumors activate the immune response to varying degrees.1,3
“What we can see is that children’s tumors 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 tumors as forcefully,” Brodin said. “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.”3
The findings suggest that future therapeutic developments should focus on improved triggering of such T cell responses. The low levels of T cell infiltration and lower average mutation rates suggest that future therapeutic developments should focus on improved triggering of such T cell responses.1,3
By understanding how children’s immune systems interact with tumors, researchers can develop targeted immunotherapies that enhance immune activation and improve treatment outcomes. These insights pave the way for advancements in pediatric cancer treatment, where therapies are designed to overcome the immune challenges faced by young patients.
