A Spatiotemporal Model of CXCL10 as a Master Regulator of Immune Evasion and Metastasis in Osteosarcoma.

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.