Spatial ligand–receptor circuits in osteosarcoma: immune resistance in bone and lung niches
- 1School of Sports Medicine and Health, Chengdu Sport University
- 2Department of Orthopedics, the Affiliated Sports Hospital of Chengdu Sport University
Abstract
Osteosarcoma (OS) has shown limited sensitivity to single-agent immune checkpoint blockade. The distribution of immune cells within bone tumors and pulmonary metastases suggests that defective tumor-cell recognition, restricted tissue access and local suppression may contribute to this resistance. This mini-review examines ligand–receptor communication between malignant cells, myeloid cells, fibroblasts and vascular or bone-associated compartments, with attention to the anatomical and experimental settings in which each interaction was studied. Human tissue profiling identifies distinct tumor interiors, myeloid-rich interfaces and fibrocollagenous boundaries, whereas perturbation studies test selected mechanisms within these compartments. GD2-dependent suppression of macrophage phagocytosis involves human SIGLEC7 or murine Siglec-E and downstream SHP2 signaling. CXCL14–integrin α11β1 signaling links OS cells to fibroblast activation and pulmonary niche formation. A separate metabolic circuit couples oxidized-lipoprotein uptake by CD36-positive fibroblasts to ANGPTL4 secretion and integrin α5β1-dependent CD8 T-cell dysfunction. CD24 and macrophage migration inhibitory factor also have OS-specific functional support, although the receptor dependencies inferred from transcriptomic data require more precise attribution. Bone-remodeling and vascular pathways are considered microenvironmental barriers rather than interchangeable immune checkpoints. We distinguish human spatial observations from cell-culture experiments, engineered bone models and animal studies, and separate experimental immune effects from clinical antitumor activity. We also consider how cell-to-tumor distances, compartment-specific receptor expression and stromal architecture could inform biomarker development. These measurements remain candidates for prospective testing rather than established criteria for treatment selection. Linking tissue localization to receptor engagement and immune function offers a route to testing which circuits sustain disease in bone, which support pulmonary dissemination and which persist across both settings.
Related
- Spatial cell-cell communication inference based on cell-spot-ligand-receptor heterogeneous graphs
- Chemokine–receptor axes in immune–tumor cell communication: spatial niches, immune exclusion, and therapy resistance
- MYC-Hyperactivated Osteosarcoma Models Exhibit Resistance to Cabozantinib plus TIGIT Blockade
- TPX2 promotes osteosarcoma progression by conferring ferroptosis resistance through the AURKA/NRF2 signaling axis
- Immune–chondrocyte ligand–receptor axes in osteoarthritis: microenvironmental control of inflammation, matrix remodeling, and chondrocyte fate
BibTeX
@article{qiu2026spatial,
title = {{Spatial ligand–receptor circuits in osteosarcoma: immune resistance in bone and lung niches}},
author = {Yijian Qiu and Shuai Deng and Junfeng Zhou and QiLin Tan and Yiyi Pan and Enchen Li and Ke Ren and Qingsong Wu},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1932933},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1932933/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Spatial ligand–receptor circuits in osteosarcoma: immune resistance in bone and lung niches
AU - Yijian Qiu
AU - Shuai Deng
AU - Junfeng Zhou
AU - QiLin Tan
AU - Yiyi Pan
AU - Enchen Li
AU - Ke Ren
AU - Qingsong Wu
PY - 2026
DA - 2026/10/20
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1932933
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1932933/full
AB - Osteosarcoma (OS) has shown limited sensitivity to single-agent immune checkpoint blockade. The distribution of immune cells within bone tumors and pulmonary metastases suggests that defective tumor-cell recognition, restricted tissue access and local suppression may contribute to this resistance. This mini-review examines ligand–receptor communication between malignant cells, myeloid cells, fibroblasts and vascular or bone-associated compartments, with attention to the anatomical and experimental settings in which each interaction was studied. Human tissue profiling identifies distinct tumor interiors, myeloid-rich interfaces and fibrocollagenous boundaries, whereas perturbation studies test selected mechanisms within these compartments. GD2-dependent suppression of macrophage phagocytosis involves human SIGLEC7 or murine Siglec-E and downstream SHP2 signaling. CXCL14–integrin α11β1 signaling links OS cells to fibroblast activation and pulmonary niche formation. A separate metabolic circuit couples oxidized-lipoprotein uptake by CD36-positive fibroblasts to ANGPTL4 secretion and integrin α5β1-dependent CD8 T-cell dysfunction. CD24 and macrophage migration inhibitory factor also have OS-specific functional support, although the receptor dependencies inferred from transcriptomic data require more precise attribution. Bone-remodeling and vascular pathways are considered microenvironmental barriers rather than interchangeable immune checkpoints. We distinguish human spatial observations from cell-culture experiments, engineered bone models and animal studies, and separate experimental immune effects from clinical antitumor activity. We also consider how cell-to-tumor distances, compartment-specific receptor expression and stromal architecture could inform biomarker development. These measurements remain candidates for prospective testing rather than established criteria for treatment selection. Linking tissue localization to receptor engagement and immune function offers a route to testing which circuits sustain disease in bone, which support pulmonary dissemination and which persist across both settings.
SN - 1664-3224
ER -