Qi Chen, Binbin Zhao, Ziyang Tan, Gustav Hedberg, Jun Wang, Laura Gonzalez, Constantin Habimana Mugabo, Anette Johnsson, Erika Negrini, Laura Piñero Páez, Lucie Rodriguez, Anna James, Yang Chen, Jaromír Mikeš, Anna Karin Bernhardsson, Stefan Markus Reitzner, Ferdinand von Walden, Olivia O’Neill, Hugo Barcenilla, Chunlin Wang, Mark M. Davis, Lena-Maria Carlson, Niklas Pal, Klas Blomgren, Dirk Repsilber, Nikolas Herold, Tadepally Lakshmikanth, Per Kogner, Linda Ljungblad, Petter Brodin.
Cell, Volume 188, Issue 5, 6 March 2025, Pages 1425-1440.e11.
Summary: 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.