2025-01-20 カロリンスカ研究所(KI)
<関連情報>
- https://news.ki.se/new-study-paves-way-for-immunotherapies-tailored-for-childhood-cancers
- https://www.cell.com/cell/fulltext/S0092-8674(24)01427-2
固形腫瘍を持つ小児におけるシステムレベルの免疫モニタリングによる精密医療の実現 Systems-level immunomonitoring in children with solid tumors to enable precision medicine
Qi Chen∙ Binbin Zhao∙ Ziyang Tan∙ … ∙ Per Kogner∙ Linda Ljungblad∙ Petter Brodin
Cell Published:January 20, 2025
DOI:https://doi.org/10.1016/j.cell.2024.12.014
Graphical abstract
Highlights
•ISAC is a population-based pediatric pan-cancer cohort of 191 children
•Systemic immunity varies by tumor type and age and differs from that in healthy children
•Tumor mutation rates vary widely and track with immune cell infiltration
•Expanded CD8+ T cell responses are rare in children but regulated like those of adult cells
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.
