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Updated: Jun 1, 2025
Predictive Immune Modeling of Solid Tumors
Published on: February 25, 2020
Systems-level immunomonitoring in children with solid tumors to enable precision medicine
Qi Chen1, Binbin Zhao1, Ziyang Tan1
1Clinical Pediatrics Unit, Department of Women's and Children's Health, Karolinska Institutet, 17165 Stockholm, Sweden.
Abstract:
Cancer is the leading cause of death from disease in children. Survival depends not only on surgery, cytostatic drugs, and radiation but also on systemic immune responses. Factors influencing these immune responses in children of different ages and tumor types are unknown. Novel immunotherapies can enhance anti-tumor immune responses, but few children have benefited, and markers of effective responses are lacking. Here, we present a systems-level analysis of immune responses in 191 children within a population-based cohort with diverse tumors and reveal that age and tumor type shape immune responses differently. Systemic inflammation and cytotoxic T cell responses correlate with tumor mutation rates and immune cell infiltration. Clonally expanded T cell responses are rarely detected in blood or tumors at diagnosis but are sometimes elicited during treatment. Expanded T cells are similarly regulated in children and adults with more immunogenic cancers. This research aims to facilitate the development of precision immunotherapies for children with cancer.
Insights
Childhood cancer survival hinges on immune responses, which vary by age and tumor type. This study reveals how systemic inflammation and T-cell activity correlate with tumor characteristics, guiding precision immunotherapy development.
Area of Science:
- Immunology
- Pediatric Oncology
- Systems Biology
Background:
- Childhood cancer is a leading cause of pediatric mortality.
- Effective cancer treatment relies on surgery, chemotherapy, radiation, and robust systemic immune responses.
- Understanding age- and tumor-specific immune responses is crucial for improving outcomes in pediatric cancer patients.
Purpose of the Study:
- To conduct a systems-level analysis of immune responses in a diverse cohort of 191 children with cancer.
- To identify factors influencing immune responses in children across different age groups and tumor types.
- To lay the groundwork for developing precision immunotherapies for pediatric cancers.
Main Methods:
- Systems-level analysis of immune responses in 191 children with diverse tumors.
- Correlation analysis of systemic inflammation and cytotoxic T-cell responses with tumor mutation rates and immune cell infiltration.
- Assessment of clonal T-cell expansion in blood and tumors at diagnosis and during treatment.
Main Results:
- Immune responses in children are significantly shaped by age and tumor type.
- Systemic inflammation and cytotoxic T-cell responses correlate with tumor mutation rates and immune cell infiltration.
- Clonally expanded T-cell responses are infrequent at diagnosis but can be induced during treatment, similar to adults with immunogenic cancers.
Conclusions:
- Age and tumor type are critical determinants of immune responses in pediatric cancer.
- Tumor mutational burden and immune infiltration are linked to systemic inflammation and cytotoxic T-cell activity.
- The findings support the development of targeted immunotherapies for children with cancer, with potential parallels to adult cancer treatment.
