Publication Date
12-27-2025
Journal
International Journal of Molecular Sciences
DOI
10.3390/ijms27010319
PMID
41516196
PMCID
PMC12785709
PubMedCentral® Posted Date
12-27-2025
PubMedCentral® Full Text Version
Post-print
Abstract
The C-X-C motif chemokine ligand 10 (CXCL10) is implicated in the progression of osteosarcoma (OS), the most aggressive pediatric bone malignancy. However, its role often presents a profound clinical paradox: although high circulating levels are strongly linked to poor prognosis, its canonical function is to recruit anti-tumor immune cells. This review unravels these contrasting roles by proposing a novel spatiotemporal model. We argue that in the early stages, immune-evading OS cells initiate the formation of a pre-metastatic niche (PMN) in the lungs, creating a localized inflammatory environment that becomes the primary source of elevated circulating CXCL10. As the disease progresses, elevated systemic levels of CXCL10 overwhelm the localized chemokine gradient at the primary tumor site, creating a potent immune decoy that diverts anti-tumor CXCR3+ T cells away from the tumor. The resulting immune desertification permits unchecked tumor growth and an increased metastatic burden. We also discuss the therapeutic implications of this model, proposing that disrupting the chemokine axis offers a roadmap for developing rational, stage-specific therapies to effectively combat metastatic OS.
Keywords
Humans, Osteosarcoma, Chemokine CXCL10, Bone Neoplasms, Animals, Tumor Microenvironment, Neoplasm Metastasis, Tumor Escape, Immune Evasion, osteosarcoma, tumor microenvironment, chemokine signaling, CXCL10, CXCR3, immune cell trafficking, pre-metastatic niche, inflammation, immune evasion, metastasis
Published Open-Access
yes
Recommended Citation
Benjamin B Gyau and Tsz-Kwong Man, "A Spatiotemporal Model of CXCL10 as a Master Regulator of Immune Evasion and Metastasis in Osteosarcoma" (2025). Faculty, Staff and Students Publications. 6252.
https://digitalcommons.library.tmc.edu/baylor_docs/6252