Spatiotemporal multi-omics uncover tumor ecosystem dynamics driving metastatic colonization

Metastatic colonization of disseminated tumor cells (DTCs) results from the failure of host innate and adaptive immunity to contain this foreign invasion. However, how DTCs interact with its tumor microenvironment (TME) during the course of distant colonization remains incompletely understood. Here, we integrated multimodal single-cell and spatial profiling combined with digital pathology to track the spatiotemporal dynamics of DTCs and their ecosystems, spanning from single-cell seeding until overt metastases, in mouse models and patient samples, and uncovered their co-evolution during metastasis process. We identified a residual and transient population of quiescent Phgdhhigh DTCs that survived innate immune clearance during seeding.