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<p>Osteosarcoma (OSA) is the most common malignant bone tumor in dogs and serves as a translational model for human pediatric OSA due to shared molecular features. This aggressive and metastatic cancer exhibits significant heterogeneity, which has limited therapeutic advances. Spatial transcriptomics offers a powerful method to investigate intratumoral complexity and the tumor microenvironment. In this study, we used the 10x Genomics Visium platform to profile spatial gene expression in 14 fresh-frozen canine OSA (cOSA) tumor samples from 11 dogs, including primary, metastatic, and recurrent tumors. Samples were stratified by survival outcomes (short-, median-, and long-term). Spatially variable genes and conserved transcriptional clusters were identified, and integration with published single-cell cOSA data enabled deconvolution of cell type proportions and spatial co-localization. Analysis of 18,834 tissue spots revealed intra-tumoral subpopulations and spatial clustering patterns. Pathways related to immune clearance were spatially enriched in long-term survivors. Deconvolution uncovered co-localization of immune cells such as mast cells with osteoclasts, and T/NK cells with regulatory dendritic cells. This study maps the spatial transcriptomic landscape of cOSA, highlighting immune microenvironment features and spatial gene expression patterns associated with survival. These findings provide insights into OSA biology and may guide future therapeutic strategies in both canine and human patients.</p>

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Spatial transcriptomic mapping of canine osteosarcoma reveals immune microenvironment features linked to survival

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月29日

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  • Rebecca Nance-Richey,
  • Leah Ackerman,
  • Dylan Ammons,
  • Ann M. Chan,
  • Valentina Stevenson,
  • Gabriela Hery,
  • Ian Hawkins,
  • Ana Herrera,
  • Alberto Riva,
  • Yanping Zhang,
  • Josephine Brown,
  • Steven W. Dow,
  • Elizabeth A. Maxwell,
  • Judit Bertran,
  • Josep Aisa,
  • Marilia Takada,
  • Michael Dark,
  • Paulo Vilar Saavedra,
  • Rowan J. Milner

摘要

Osteosarcoma (OSA) is the most common malignant bone tumor in dogs and serves as a translational model for human pediatric OSA due to shared molecular features. This aggressive and metastatic cancer exhibits significant heterogeneity, which has limited therapeutic advances. Spatial transcriptomics offers a powerful method to investigate intratumoral complexity and the tumor microenvironment. In this study, we used the 10x Genomics Visium platform to profile spatial gene expression in 14 fresh-frozen canine OSA (cOSA) tumor samples from 11 dogs, including primary, metastatic, and recurrent tumors. Samples were stratified by survival outcomes (short-, median-, and long-term). Spatially variable genes and conserved transcriptional clusters were identified, and integration with published single-cell cOSA data enabled deconvolution of cell type proportions and spatial co-localization. Analysis of 18,834 tissue spots revealed intra-tumoral subpopulations and spatial clustering patterns. Pathways related to immune clearance were spatially enriched in long-term survivors. Deconvolution uncovered co-localization of immune cells such as mast cells with osteoclasts, and T/NK cells with regulatory dendritic cells. This study maps the spatial transcriptomic landscape of cOSA, highlighting immune microenvironment features and spatial gene expression patterns associated with survival. These findings provide insights into OSA biology and may guide future therapeutic strategies in both canine and human patients.