Single-cell spatial analysis of pediatric high-grade glioma reveals a novel population of SPP1+/GPNMB+ myeloid cells with immunosuppressive and tumor-promoting capabilities Article Swipe
Thijs J M van den Broek
,
Raoull Hoogendijk
,
Mariëtte E.G. Kranendonk
,
Julie A S Lammers
,
A. Krishnamoorthy
,
Ravian L. van Ineveld
,
Milo Molleson
,
Vasily O. Tsvetkov
,
Femke Ringnalda
,
Marc van de Wetering
,
Yan Su
,
John Bianco
,
Cristian Ruiz-Moreno
,
Mario Ries
,
Eelco W. Hoving
,
Jasper van der Lugt
,
Leila Akkari
,
David P. Schrijver
,
Hendrik G. Stunnenberg
,
Anne C. Rios
,
Dannis G van Vuurden
,
Anoek Zomer
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1093/neuped/wuaf002
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1093/neuped/wuaf002
Background Pediatric-type diffuse high-grade gliomas (pHGGs) are a leading cause of pediatric cancer-related mortality. Although immunotherapy offers a promising treatment avenue, clinical responses in pHGG patients remain limited. A detailed understanding of the tumor immune microenvironment (TIME) is essential for advancing immunotherapeutic strategies. Methods We performed single-cell spatial analysis integrating cyclical immunofluorescence imaging and spatial molecular imaging to interrogate the proteomic and transcriptomic landscape of pHGGs. A tissue microarray comprising 32 diagnostic patient-derived pHGG samples was utilized to map the spatial distribution of immune and tumor cells. Results Our analyses reveal that the pHGG TIME is predominantly composed of myeloid cells, including brain-resident microglia and monocyte-derived macrophages, with only few T cells. A significant subset of these myeloid cells expresses mesenchymal (MES)-like genes and is positive for SPP1 and GPNMB. Spatial mapping further demonstrated that SPP1+/GPNMB+ myeloid cells localize in close proximity to MES-like tumor cells, and negatively correlate with the location and presence of CD8+ T cells. These cells also express genes related to immunosuppression and epithelial-to-mesenchymal transition, indicating their potential role in establishing an immunosuppressive niche. Conclusions Our findings reveal a distinct immune landscape in pHGGs characterized by SPP1+/GPNMB+ myeloid cells which may contribute to the exclusion of CD8+ T cells. This spatially resolved insight identifies these myeloid cells as promising therapeutic targets and provides a rationale for developing novel immunotherapeutic strategies to improve outcomes in pediatric high-grade gliomas.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/neuped/wuaf002
- OA Status
- hybrid
- References
- 95
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4414050161
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4414050161Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1093/neuped/wuaf002Digital Object Identifier
- Title
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Single-cell spatial analysis of pediatric high-grade glioma reveals a novel population of SPP1+/GPNMB+ myeloid cells with immunosuppressive and tumor-promoting capabilitiesWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-07-01Full publication date if available
- Authors
-
Thijs J M van den Broek, Raoull Hoogendijk, Mariëtte E.G. Kranendonk, Julie A S Lammers, A. Krishnamoorthy, Ravian L. van Ineveld, Milo Molleson, Vasily O. Tsvetkov, Femke Ringnalda, Marc van de Wetering, Yan Su, John Bianco, Cristian Ruiz-Moreno, Mario Ries, Eelco W. Hoving, Jasper van der Lugt, Leila Akkari, David P. Schrijver, Hendrik G. Stunnenberg, Anne C. Rios, Dannis G van Vuurden, Anoek ZomerList of authors in order
- Landing page
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https://doi.org/10.1093/neuped/wuaf002Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1093/neuped/wuaf002Direct OA link when available
- Cited by
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0Total citation count in OpenAlex
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95Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.positive | 126 |
| abstract_inverted_index.presence | 154 |
| abstract_inverted_index.provides | 217 |
| abstract_inverted_index.resolved | 206 |
| abstract_inverted_index.utilized | 77 |
| abstract_inverted_index.advancing | 41 |
| abstract_inverted_index.correlate | 149 |
| abstract_inverted_index.essential | 39 |
| abstract_inverted_index.exclusion | 199 |
| abstract_inverted_index.expresses | 120 |
| abstract_inverted_index.including | 102 |
| abstract_inverted_index.landscape | 64, 186 |
| abstract_inverted_index.microglia | 104 |
| abstract_inverted_index.molecular | 56 |
| abstract_inverted_index.pediatric | 12, 229 |
| abstract_inverted_index.performed | 46 |
| abstract_inverted_index.potential | 172 |
| abstract_inverted_index.promising | 19, 213 |
| abstract_inverted_index.proteomic | 61 |
| abstract_inverted_index.proximity | 142 |
| abstract_inverted_index.rationale | 219 |
| abstract_inverted_index.responses | 23 |
| abstract_inverted_index.spatially | 205 |
| abstract_inverted_index.treatment | 20 |
| abstract_inverted_index.(MES)-like | 122 |
| abstract_inverted_index.Background | 1 |
| abstract_inverted_index.comprising | 70 |
| abstract_inverted_index.contribute | 196 |
| abstract_inverted_index.developing | 221 |
| abstract_inverted_index.diagnostic | 72 |
| abstract_inverted_index.high-grade | 4, 230 |
| abstract_inverted_index.identifies | 208 |
| abstract_inverted_index.indicating | 170 |
| abstract_inverted_index.microarray | 69 |
| abstract_inverted_index.mortality. | 14 |
| abstract_inverted_index.negatively | 148 |
| abstract_inverted_index.strategies | 224 |
| abstract_inverted_index.Conclusions | 179 |
| abstract_inverted_index.integrating | 50 |
| abstract_inverted_index.interrogate | 59 |
| abstract_inverted_index.mesenchymal | 121 |
| abstract_inverted_index.significant | 114 |
| abstract_inverted_index.single-cell | 47 |
| abstract_inverted_index.strategies. | 43 |
| abstract_inverted_index.therapeutic | 214 |
| abstract_inverted_index.transition, | 169 |
| abstract_inverted_index.SPP1+/GPNMB+ | 136, 191 |
| abstract_inverted_index.demonstrated | 134 |
| abstract_inverted_index.distribution | 82 |
| abstract_inverted_index.establishing | 175 |
| abstract_inverted_index.macrophages, | 107 |
| abstract_inverted_index.characterized | 189 |
| abstract_inverted_index.immunotherapy | 16 |
| abstract_inverted_index.predominantly | 97 |
| abstract_inverted_index.understanding | 31 |
| abstract_inverted_index.Pediatric-type | 2 |
| abstract_inverted_index.cancer-related | 13 |
| abstract_inverted_index.transcriptomic | 63 |
| abstract_inverted_index.patient-derived | 73 |
| abstract_inverted_index.brain-resident | 103 |
| abstract_inverted_index.microenvironment | 36 |
| abstract_inverted_index.monocyte-derived | 106 |
| abstract_inverted_index.immunosuppression | 166 |
| abstract_inverted_index.immunosuppressive | 177 |
| abstract_inverted_index.immunotherapeutic | 42, 223 |
| abstract_inverted_index.immunofluorescence | 52 |
| abstract_inverted_index.epithelial-to-mesenchymal | 168 |
| cited_by_percentile_year | |
| countries_distinct_count | 2 |
| institutions_distinct_count | 22 |
| citation_normalized_percentile.value | 0.43497443 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |