MINI REVIEW article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1640645
This article is part of the Research TopicExploring immune low-response states through single-cell technologies and spatial transcriptomicsView all 11 articles
Deciphering spatially confined immune evasion niches in osteosarcoma with 3-D spatial transcriptomics: A literature review
Provisionally accepted
- The Affiliated Hospital of Southwest Medical University, Luzhou, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Osteosarcoma (OS) is the most common primary malignant bone tumour of childhood, yet five-year survival has plateaued at ~60–70 % for localised disease and plunges below 30 % once metastasis emerges. Formerly viewed as a cell-intrinsic neoplasm entombed in mineralised bone, OS is now understood as a spatially stratified ecosystem whose immune-evasion niches choreograph progression. Three-dimensional spatial transcriptomics (3-D ST) fuses barcode-based transcript capture with volumetric reconstruction, preserving x-, y- and z-axis context and exposing concentric C1QC necrotic belts, MCAM (melanoma cell-adhesion molecule, CD146) peri-vascular corridors, hypoxic glycolytic rims and therapy-induced tertiary-lymphoid islets that collectively sequester cytotoxic lymphocytes. Pre-clinical atlases link PD-L1 high SOX9 stem-like cells, LGALS3 macrophages and VEGFA-driven endothelial tips to chemoresistance and immune-checkpoint failure, while ligand–receptor inference highlights VEGFA–VEGFR2, CXCL12–CXCR4 and complement–CSF1R axes as actionable bottlenecks. Translational efforts already echo these insights: dual MCAM/VEGFR blockade collapses vascular gates, C1s or CSF1R antagonists dismantle necrotic-core “cold pockets”, and MCT1–POSTN combinations target lactate-stiffened stromal shells. By weaving methodological advances with emergent biology, this review crystallises how 3-D ST redefines OS immunopathology, sharpens biomarker discovery and accelerates spatially guided combination therapies. We aim to expose diagnostic blind spots, spotlight niche-directed interventions and chart a roadmap toward lifting the long-standing therapeutic ceiling in osteosarcoma.
Keywords: Osteosarcoma, Spatial transcriptomics, 3-D mapping, tumour microenvironment, Immune Evasion, tumour-associated macrophages
Received: 04 Jun 2025; Accepted: 26 Jun 2025.
Copyright: © 2025 Wan, Qiu, Tang, Zuo and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yongxian Wan, The Affiliated Hospital of Southwest Medical University, Luzhou, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.