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

Francisca J. Bergsma; Jan Koster; Bob Baalman; Francis Mussai; Hubert N. Caron; Jan J. Molenaar; Judith Wienke

doi:10.1016/j.ejca.2025.115708

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

Francisca J. Bergsma
, Jan Koster
, Bob Baalman
, Francis Mussai
, Hubert N. Caron
, Jan J. Molenaar
, Judith Wienke^*

^*Corresponding author for this work

Princess Máxima Center for Pediatric Oncology
University of Amsterdam
Birmingham Women's and Children's NHS Foundation Trust
F. Hoffmann-La Roche AG
Utrecht University

Research output: Contribution to journal › Review article › Academic › peer-review

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Abstract

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.

Original language	English
Article number	115708
Journal	Eur. J. Cancer
Volume	228
DOIs	https://doi.org/10.1016/j.ejca.2025.115708
Publication status	Published - 1 Oct 2025

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Immune landscape
Immunohistochemistry
Pediatric solid tumors
Single-cell RNA sequencing
Systematic review

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

abstract = "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.",

keywords = "Immune landscape, Immunohistochemistry, Pediatric solid tumors, Single-cell RNA sequencing, Systematic review",

author = "Bergsma, \{Francisca J.\} and Jan Koster and Bob Baalman and Francis Mussai and Caron, \{Hubert N.\} and Molenaar, \{Jan J.\} and Judith Wienke",

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doi = "10.1016/j.ejca.2025.115708",

language = "English",

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T1 - The immune landscape of pediatric (extra)cranial solid tumors

T2 - A systematic review and integration of immunohistochemistry and single-cell RNA sequencing data

AU - Bergsma, Francisca J.

AU - Koster, Jan

AU - Baalman, Bob

AU - Mussai, Francis

AU - Caron, Hubert N.

AU - Molenaar, Jan J.

AU - Wienke, Judith

PY - 2025/10/1

Y1 - 2025/10/1

N2 - 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.

AB - 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.

KW - Immune landscape

KW - Immunohistochemistry

KW - Pediatric solid tumors

KW - Single-cell RNA sequencing

KW - Systematic review

UR - https://www.scopus.com/pages/publications/105013999000

U2 - 10.1016/j.ejca.2025.115708

DO - 10.1016/j.ejca.2025.115708

M3 - Review article

C2 - 40857838

SN - 0959-8049

VL - 228

JO - Eur. J. Cancer

JF - Eur. J. Cancer

M1 - 115708

ER -

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

Abstract

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Keywords

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