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Review Open Access

Tumor microenvironment in bone sarcomas: Implications for immunotherapy and emerging therapeutic vulnerabilities (Review)

  • Authors:
    • Wentao Li
    • Lijun Lv
    • Yibin Jin
    • Xin Yuan
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedic Surgery, The Third Affiliated Hospital of Gansu University of Chinese Medicine, Baiyin, Gansu 730900, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 45
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    Published online on: January 16, 2026
       https://doi.org/10.3892/or.2026.9050
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Abstract

Bone sarcomas remain lethal despite multimodal therapy, primarily because the mineralized, immunosuppressive tumor microenvironment (TME) promotes chemo‑ and immune‑resistance. Integrating single‑cell and spatial omics across osteosarcoma, Ewing sarcoma and chondrosarcoma delineates subtype‑specific TME archetypes dominated by M2 macrophages, exhausted T cells and a stiff extracellular matrix. Mechanistic dissection reveals tractable vulnerabilities, myeloid reprogramming, extracellular matrix modulation and metabolic and epigenetic checkpoints, that can be targeted with bone‑selective delivery systems and biomarker‑driven combination trials to convert therapeutic failure into durable remission. Therefore, the aim of the present review is to synthesize the latest single‑cell, spatial and functional data to map bone‑sarcoma TME heterogeneity, dissect resistance mechanisms and propose integrated, biomarker‑guided therapeutic strategies that can be translated into treatments.

View Figures

Figure 1

A schematic diagram illustrating the
characteristics of the tumor microenvironment in bone sarcoma
(figure was created using the online graphic design website
Figdraw: www.figdraw.com). TAM,
tumor-associated macrophage; CAF, cancer-associated fibroblast;
ECM, extracellular matrix; PD-L1, programmed death-ligand 1; IDO1,
indoleamine 2,3-dioxygenase 1; MDSCs, myeloid-derived suppressor
cells; NK, natural killer; Tregs, T-regulatory cells; HIF-1α,
hypoxia inducible factor-1α; TIM-3,0T-cell Immunoglobulin and
Mucin-domain containing-3.

Figure 2

Mechanisms of immunosuppression
within the bone sarcoma TME (The figure was created using the
online graphic design website Figdraw: www.figdraw.com). TAM, tumor-associated macrophage;
Treg, regulatory T cell; MDSCs, myeloid-derived suppressor cells;
CAFs, cancer-associated fibroblasts; ECM, extracellular matrix;
PD-L1, programmed death-ligand 1; TIM-3, T-cell immunoglobulin and
mucin-domain containing-3; LAG-3, lymphocyte-activation gene 3;
IDO1, indoleamine 2,3-dioxygenase 1; ARG1, arginase-1; HIF-1α,
hypoxia-inducible factor-1 α; ADO, adenosine; KYN, kynurenine; AhR,
aryl hydrocarbon receptor; cDC1, conventional type 1 dendritic
cell.
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Copy and paste a formatted citation
Spandidos Publications style
Li W, Lv L, Jin Y and Yuan X: <p>Tumor microenvironment in bone sarcomas: Implications for immunotherapy and emerging therapeutic vulnerabilities (Review)</p>. Oncol Rep 55: 45, 2026.
APA
Li, W., Lv, L., Jin, Y., & Yuan, X. (2026). <p>Tumor microenvironment in bone sarcomas: Implications for immunotherapy and emerging therapeutic vulnerabilities (Review)</p>. Oncology Reports, 55, 45. https://doi.org/10.3892/or.2026.9050
MLA
Li, W., Lv, L., Jin, Y., Yuan, X."<p>Tumor microenvironment in bone sarcomas: Implications for immunotherapy and emerging therapeutic vulnerabilities (Review)</p>". Oncology Reports 55.3 (2026): 45.
Chicago
Li, W., Lv, L., Jin, Y., Yuan, X."<p>Tumor microenvironment in bone sarcomas: Implications for immunotherapy and emerging therapeutic vulnerabilities (Review)</p>". Oncology Reports 55, no. 3 (2026): 45. https://doi.org/10.3892/or.2026.9050
Copy and paste a formatted citation
x
Spandidos Publications style
Li W, Lv L, Jin Y and Yuan X: <p>Tumor microenvironment in bone sarcomas: Implications for immunotherapy and emerging therapeutic vulnerabilities (Review)</p>. Oncol Rep 55: 45, 2026.
APA
Li, W., Lv, L., Jin, Y., & Yuan, X. (2026). <p>Tumor microenvironment in bone sarcomas: Implications for immunotherapy and emerging therapeutic vulnerabilities (Review)</p>. Oncology Reports, 55, 45. https://doi.org/10.3892/or.2026.9050
MLA
Li, W., Lv, L., Jin, Y., Yuan, X."<p>Tumor microenvironment in bone sarcomas: Implications for immunotherapy and emerging therapeutic vulnerabilities (Review)</p>". Oncology Reports 55.3 (2026): 45.
Chicago
Li, W., Lv, L., Jin, Y., Yuan, X."<p>Tumor microenvironment in bone sarcomas: Implications for immunotherapy and emerging therapeutic vulnerabilities (Review)</p>". Oncology Reports 55, no. 3 (2026): 45. https://doi.org/10.3892/or.2026.9050
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