Spatial immune profiling reveals lymphocyte confinement to myeloid-mesenchymal niches and heterogeneous therapeutic T-cell opportunity in pediatric ependymoma
- 1Karolinska Institutet
Abstract
Pediatric posterior fossa group A (PFA) ependymoma is an aggressive, chemo-resistant brain tumor with a poor 10-year overall survival and no therapeutic options at relapse. Although conventionally classified as immune-cold, the spatial organization and therapeutic relevance of its rare immune infiltrates remain poorly characterized. Here, we present a spatially resolved immune analysis of 14 PFA ependymoma sections using published Visium spatial transcriptomics data analyzed through a multi-stage immune-focused computational framework combining reference-guided deconvolution, functional lymphocyte state scoring, ligand-receptor inference, and {beta}/{gamma}{delta} T cell immunotherapy opportunity scoring. Lymphocyte-associated hotspots were identified in 6 of 14 sections and, among confidently classified hotspots, were dominated by inflammatory-associated and retention-associated transcriptional states rather than cytotoxic or exhausted programs. These hotspots were preferentially confined to myeloid- and mesenchymal-rich tumor zones with near-complete exclusion from epithelial regions; ligand-receptor analysis identified four candidate restriction axes (SPP1-CD44, FN1-integrin, collagen VI-integrin, and APP-CD74). Immunotherapy opportunity scoring revealed heterogeneous and spatially compartmentalized {beta} and {gamma}{delta} T cell recognition landscapes across sections: {beta}T ligand availability and immunosuppressive tone both rose in the mesenchymal compartment, while the two components of {gamma}{delta} phosphoantigen-mediated recognition were spatially and transcriptionally dissociated from one another. Together, these findings reframe PFA ependymoma not as a monolithic immune desert but as a tumor type with spatially compartmentalized, mechanistically tractable immune niches, and provide a generalizable computational strategy for mapping immune architecture and T cell therapy susceptibility in low-infiltrated pediatric CNS tumors.
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BibTeX
@misc{truong2026spatial,
title = {{Spatial immune profiling reveals lymphocyte confinement to myeloid-mesenchymal niches and heterogeneous therapeutic T-cell opportunity in pediatric ependymoma}},
author = {P. Truong and R. Mirzazadeh and J. Lundeberg and K. Blomgren and L. Boutin},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.24.754209},
url = {https://www.biorxiv.org/content/10.64898/2026.09.24.754209v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Spatial immune profiling reveals lymphocyte confinement to myeloid-mesenchymal niches and heterogeneous therapeutic T-cell opportunity in pediatric ependymoma
AU - P. Truong
AU - R. Mirzazadeh
AU - J. Lundeberg
AU - K. Blomgren
AU - L. Boutin
PY - 2026
DA - 2026/09/24
PB - bioRxiv
DO - 10.64898/2026.09.24.754209
UR - https://www.biorxiv.org/content/10.64898/2026.09.24.754209v1
AB - Pediatric posterior fossa group A (PFA) ependymoma is an aggressive, chemo-resistant brain tumor with a poor 10-year overall survival and no therapeutic options at relapse. Although conventionally classified as immune-cold, the spatial organization and therapeutic relevance of its rare immune infiltrates remain poorly characterized. Here, we present a spatially resolved immune analysis of 14 PFA ependymoma sections using published Visium spatial transcriptomics data analyzed through a multi-stage immune-focused computational framework combining reference-guided deconvolution, functional lymphocyte state scoring, ligand-receptor inference, and {beta}/{gamma}{delta} T cell immunotherapy opportunity scoring. Lymphocyte-associated hotspots were identified in 6 of 14 sections and, among confidently classified hotspots, were dominated by inflammatory-associated and retention-associated transcriptional states rather than cytotoxic or exhausted programs. These hotspots were preferentially confined to myeloid- and mesenchymal-rich tumor zones with near-complete exclusion from epithelial regions; ligand-receptor analysis identified four candidate restriction axes (SPP1-CD44, FN1-integrin, collagen VI-integrin, and APP-CD74). Immunotherapy opportunity scoring revealed heterogeneous and spatially compartmentalized {beta} and {gamma}{delta} T cell recognition landscapes across sections: {beta}T ligand availability and immunosuppressive tone both rose in the mesenchymal compartment, while the two components of {gamma}{delta} phosphoantigen-mediated recognition were spatially and transcriptionally dissociated from one another. Together, these findings reframe PFA ependymoma not as a monolithic immune desert but as a tumor type with spatially compartmentalized, mechanistically tractable immune niches, and provide a generalizable computational strategy for mapping immune architecture and T cell therapy susceptibility in low-infiltrated pediatric CNS tumors.
ER -