Systems-level immunomonitoring in children with solid tumors to enable precision medicine

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.