The immune landscape of pediatric (extra)cranial solid tumors: A systematic review and integration of immunohistochemistry and single-cell RNA sequencing data

Background Immunotherapies achieved remarkable success in adult cancers, yet their efficacy in pediatric brain and extracranial solid tumors remains limited. Insights into the unique immune landscape of pediatric tumors are crucial to improve immunotherapies for pediatric patients. Methods We performed a systematic search for studies reporting immunohistochemistry (IHC), single-cell- or single-nucleus RNA-sequencing (sc/snSeq) data on the immune landscape of pediatric tumors. For IHC studies, data on macrophages, T cells, T helper cells, regulatory T cells, NK cells and B cells were extracted. For sc/snSeq studies, cell cluster counts were extracted. 47 IHC studies (2187 tumor samples) and 26 sc/snSeq studies (272 tumor samples) were included in the analysis. Results Our integrative in-depth analysis of 73 studies covered 35 unique pediatric tumor types with 17 tumor types analyzed by IHC, 4 by sc/snSeq, and 13 by both techniques. Regardless of variability in analysis methods, both IHC and sc/snSeq showed that peripheral nerve tumors and soft tissue sarcomas had relatively immune-infiltrated, T cell-rich tumor microenvironments (TME). Brain tumors exhibited a macrophage/microglia-rich, NK cell-infiltrated and T cell-depleted TME. Sc/snSeq data confirmed these observations, showing a macrophage/microglia-rich brain TME. Compared to adult tumors, (CD8 + ) T cell infiltration and macrophage infiltration was low for all pediatric tumor types. Integrated IHC data was visualized in interactive heatmaps, publicly available on R2 as a comprehensive atlas [https://hgserver1.amc.nl/cgi-bin/r2/main.cgi?option=imi2_targetmap_v1; map Immune_landscape_mm2(by patient)_v4]. Conclusion We provide a comprehensive, integrated overview of the immune landscape of pediatric (extra)cranial solid tumors. These insights can aid the development and selection of immunotherapeutic strategies for specific pediatric cancers, tailored to their unique immune characteristics.