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

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.