ReviewFrontiers in cell and developmental biology2026
From vascular normalization to VEGF-independent escape: multi-omics-defined angio-immune ecosystem states.
Review in Frontiers in cell and developmental biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Anti-angiogenic therapy and immune checkpoint blockade can synergize, yet benefits are frequently transient, implying that resistance reflects ecosystem-level reprogramming rather than failure of a single pathway. Here we define angio-immune ecosystem states as reproducible tumor microenvironment configurations that couple vascular function, immune composition, and spatial architecture. We summarize four resistance-associated states: endothelial-stromal gatekeeping with immune exclusion, a time-limited normalization window, hypoxia/myeloid-driven rebound immunosuppression, and VEGF-independent perfusion escape via vessel co-option, vasculogenic mimicry, or intussusceptive remodeling. Finally, we propose an interpretable measurement stack, integrating bulk transcriptional modules, single-cell-anchored cell-state programs, and spatial neighborhood features, to enable cross-cohort stratification and longitudinal tracking. This framework supports state-matched combinations by linking therapeutic resistance to distinct spatial configurations of the intravascular lumen, endothelial interface, perivascular niche, stromal-parenchymal boundary, and immune-cell trafficking axis.
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