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Spatial transcriptomics exploration of the primary neuroblastoma microenvironment in archived FFPE samples unveils novel paracrine interactions

Siaw, Joachim T LU orcid ; Merseburger, Peter ; Borenäs, Marcus ; Jansson, Caroline LU ; Karlsson, Jenny LU ; Claeys, Arne ; Jennische, Eva ; Lind, Dan E ; Gisselsson Nord, David LU and Palmer, Ruth H , et al. (2025) In Journal of Pathology
Abstract

High-risk neuroblastomas exhibit a high degree of intratumoral heterogeneity. Single-cell RNA sequencing has greatly improved our understanding of these tumors, but the method lacks cellular tissue context and spatial information about local signaling dynamics. To address this, we profiled untreated and chemotherapy-treated high-risk neuroblastomas from archived, formalin-fixed, paraffin-embedded (FFPE) tissues from two patients using spatial transcriptomics. We confirmed the transcriptional and cellular heterogeneous nature of the neuroblastoma microenvironment and identified several unique spatial niches and patterns. In one of the treated tumors, a spatially constrained cluster of undifferentiated and 11p-gained cancer cells was... (More)

High-risk neuroblastomas exhibit a high degree of intratumoral heterogeneity. Single-cell RNA sequencing has greatly improved our understanding of these tumors, but the method lacks cellular tissue context and spatial information about local signaling dynamics. To address this, we profiled untreated and chemotherapy-treated high-risk neuroblastomas from archived, formalin-fixed, paraffin-embedded (FFPE) tissues from two patients using spatial transcriptomics. We confirmed the transcriptional and cellular heterogeneous nature of the neuroblastoma microenvironment and identified several unique spatial niches and patterns. In one of the treated tumors, a spatially constrained cluster of undifferentiated and 11p-gained cancer cells was identified, surrounded by a rim of macrophages. A signaling interaction between the chemokine CCL18 and its receptor PITPNM3 was predicted between these cells. In the other tumor, we identified a stromal cluster with high transcriptional similarity to the adrenal cortex. These adrenocortical-like cells expressed several oncogenic ligand-encoding genes (e.g. ALKAL2 and NRTN), which were predicted to communicate with neighboring cancer cells that expressed the corresponding receptors (e.g. ALK, RET). Several of these interactions were further validated experimentally and were shown to be clinically relevant. Collectively, our spatial analysis identifies multiple previously unrecognized signaling axes that may offer novel therapeutic options in neuroblastoma. 

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Contribution to journal
publication status
epub
subject
in
Journal of Pathology
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:105012719406
  • pmid:40778592
ISSN
0022-3417
DOI
10.1002/path.6457
language
English
LU publication?
yes
additional info
© 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
id
30b2c121-eef7-4395-80d4-8eccb34a3c55
date added to LUP
2025-08-13 13:34:50
date last changed
2025-08-14 14:10:12
@article{30b2c121-eef7-4395-80d4-8eccb34a3c55,
  abstract     = {{<p>High-risk neuroblastomas exhibit a high degree of intratumoral heterogeneity. Single-cell RNA sequencing has greatly improved our understanding of these tumors, but the method lacks cellular tissue context and spatial information about local signaling dynamics. To address this, we profiled untreated and chemotherapy-treated high-risk neuroblastomas from archived, formalin-fixed, paraffin-embedded (FFPE) tissues from two patients using spatial transcriptomics. We confirmed the transcriptional and cellular heterogeneous nature of the neuroblastoma microenvironment and identified several unique spatial niches and patterns. In one of the treated tumors, a spatially constrained cluster of undifferentiated and 11p-gained cancer cells was identified, surrounded by a rim of macrophages. A signaling interaction between the chemokine CCL18 and its receptor PITPNM3 was predicted between these cells. In the other tumor, we identified a stromal cluster with high transcriptional similarity to the adrenal cortex. These adrenocortical-like cells expressed several oncogenic ligand-encoding genes (e.g. ALKAL2 and NRTN), which were predicted to communicate with neighboring cancer cells that expressed the corresponding receptors (e.g. ALK, RET). Several of these interactions were further validated experimentally and were shown to be clinically relevant. Collectively, our spatial analysis identifies multiple previously unrecognized signaling axes that may offer novel therapeutic options in neuroblastoma. </p>}},
  author       = {{Siaw, Joachim T and Merseburger, Peter and Borenäs, Marcus and Jansson, Caroline and Karlsson, Jenny and Claeys, Arne and Jennische, Eva and Lind, Dan E and Gisselsson Nord, David and Palmer, Ruth H and Van den Eynden, Jimmy}},
  issn         = {{0022-3417}},
  language     = {{eng}},
  month        = {{08}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Journal of Pathology}},
  title        = {{Spatial transcriptomics exploration of the primary neuroblastoma microenvironment in archived FFPE samples unveils novel paracrine interactions}},
  url          = {{http://dx.doi.org/10.1002/path.6457}},
  doi          = {{10.1002/path.6457}},
  year         = {{2025}},
}