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<p>Osteosarcoma is characterized by extensive inter- and intra-tumoral heterogeneity, contributing to treatment resistance and poor outcomes. Here, we present a comprehensive spatial transcriptomics analysis of osteosarcoma, encompassing primary tumors and local or metastatic relapses across diverse phenotypic subtypes. Despite this heterogeneity, we identify a nine-gene cell surface signature with theranostic potential, validated in independent datasets and shown by immunohistochemistry to be distributed across distinct tumor compartments, supporting multi-targeted therapeutic strategies. Analysis of the tumor immune microenvironment reveals systematic lymphoid exclusion, differential myeloid infiltration patterns, and a type I interferon response signature that may explain the failure of IFN-α supplementation in prior trials. Notably, we provide evidence of monocyte-derived osteoclastic differentiation within human osteosarcoma lung metastases, identifying precursor populations with complex secretory phenotypes representing potential immunomodulatory targets. This study offers biological insights and translational opportunities while providing a resource for the osteosarcoma research community.</p>

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Spatial transcriptomic atlas of aggressive osteosarcomas reveals shared immune landscape and targetable surface markers

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月3日

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  • Gaël Moquin-Beaudry,
  • Maria Eugénia Marques Da Costa,
  • Pierre Khneisser,
  • Corentin Thuilliez,
  • Baptiste Audinot,
  • Hanane Zair,
  • Nicolas Signolle,
  • Michael McDermott,
  • Marie-Dominique Tabone,
  • Jean-Yves Scoazec,
  • Cécile Badoual,
  • Birgit Geoerger,
  • Damien Drubay,
  • Nathalie Gaspar,
  • Antonin Marchais

摘要

Osteosarcoma is characterized by extensive inter- and intra-tumoral heterogeneity, contributing to treatment resistance and poor outcomes. Here, we present a comprehensive spatial transcriptomics analysis of osteosarcoma, encompassing primary tumors and local or metastatic relapses across diverse phenotypic subtypes. Despite this heterogeneity, we identify a nine-gene cell surface signature with theranostic potential, validated in independent datasets and shown by immunohistochemistry to be distributed across distinct tumor compartments, supporting multi-targeted therapeutic strategies. Analysis of the tumor immune microenvironment reveals systematic lymphoid exclusion, differential myeloid infiltration patterns, and a type I interferon response signature that may explain the failure of IFN-α supplementation in prior trials. Notably, we provide evidence of monocyte-derived osteoclastic differentiation within human osteosarcoma lung metastases, identifying precursor populations with complex secretory phenotypes representing potential immunomodulatory targets. This study offers biological insights and translational opportunities while providing a resource for the osteosarcoma research community.