Spatial profiling identifies regionally distinct microenvironments and targetable immunosuppressive mechanisms in pediatric osteosarcoma pulmonary metastases Article Swipe
Jason Eigenbrood
,
Nathan Wong
,
Paul Mallory
,
Jorge A. Pereira
,
DreeAnna Morris
,
Jessica A. Beck
,
James C. Cronk
,
Carly M. Sayers
,
Monica Mendez
,
Linus Kaiser
,
Julie Galindo
,
Jatinder Singh
,
Ashley Cardamone
,
Milind Pore
,
Michael C. Kelly
,
Amy K. LeBlanc
,
Jennifer Cotter
,
Rosandra N. Kaplan
,
Troy A. McEachron
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.01.22.631350
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.01.22.631350
Osteosarcoma is the most common malignant bone tumor in young patients and remains a significant clinical challenge, particularly in the context of metastatic disease. Despite extensive documentation of genomic alterations in osteosarcoma, studies detailing the immunosuppressive mechanisms within the metastatic osteosarcoma microenvironment are lacking. Our objective was to characterize the spatial transcriptional landscape of metastatic osteosarcoma to reveal these immunosuppressive mechanisms and identify promising therapeutic targets. Here, we performed spatial transcriptional profiling on a cohort of osteosarcoma pulmonary metastases from pediatric patients. We reveal a conserved spatial gene expression pattern resembling a foreign body granuloma, characterized by peripheral inflammatory signaling, fibrocollagenous encapsulation, lymphocyte exclusion, and peritumoral macrophage accumulation. We also show that the intratumoral microenvironment of these lesions lack inflammatory signaling. Additionally, we identified CXCR4 as an actionable immunomodulatory target that bridges both the intratumoral and extratumoral microenvironments and highlights the spatial heterogeneity and complexity of this pathway. Collectively, this study reveals that metastatic osteosarcoma specimens are comprised of multiple regionally distinct immunosuppressive microenvironments.
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- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.01.22.631350
- OA Status
- green
- References
- 84
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4406786944
All OpenAlex metadata
Raw OpenAlex JSON
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- DOI
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https://doi.org/10.1101/2025.01.22.631350Digital Object Identifier
- Title
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Spatial profiling identifies regionally distinct microenvironments and targetable immunosuppressive mechanisms in pediatric osteosarcoma pulmonary metastasesWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-01-24Full publication date if available
- Authors
-
Jason Eigenbrood, Nathan Wong, Paul Mallory, Jorge A. Pereira, DreeAnna Morris, Jessica A. Beck, James C. Cronk, Carly M. Sayers, Monica Mendez, Linus Kaiser, Julie Galindo, Jatinder Singh, Ashley Cardamone, Milind Pore, Michael C. Kelly, Amy K. LeBlanc, Jennifer Cotter, Rosandra N. Kaplan, Troy A. McEachronList of authors in order
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https://doi.org/10.1101/2025.01.22.631350Publisher landing page
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1101/2025.01.22.631350Direct OA link when available
- Concepts
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Osteosarcoma, Profiling (computer programming), Medicine, Cancer research, Oncology, Computer science, Operating systemTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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84Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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