Decoding the spatiotemporal dynamics of tumor immune niche remodeling in cancer immunotherapy

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

The tumor immune niche (TIN) is a dynamic, spatially organized compartment that orchestrates immunotherapy response and resistance. Despite the clinical success of immune checkpoint inhibitors and CAR-T therapies, the TIN's inherent immunosuppressive properties and adaptive plasticity drive significant therapeutic resistance. This review systematically decodes the spatiotemporal remodeling of the TIN-encompassing aberrant vasculature, dense extracellular matrix barriers, and metabolic competition-during various immunotherapeutic interventions. We highlight core biological processes driving this transformation, including the spatiotemporal coupling of vascular normalization with T-cell infiltration, metabolic functional switching, and myeloid cell phenotypic plasticity. Furthermore, we synthesize clinical evidence identifying molecular and spatial hallmarks of responsive versus resistant niches. Finally, we discuss how emerging single-cell spatiotemporal omics and physio-mimetic organoid models can deconstruct niche heterogeneity to inform personalized, precision combinatorial strategies for durable tumor control.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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