Spatiotemporal Profiling of Patient Derived Xenograft Tumor Microenvironments

Wanying Li

Document Type

Article

Publication Date

2025

Keywords

JGM

Abstract

Tumors develop within a complex cellular environment that influences their growth and response to therapy. While this tumor microenvironment (TME) is known to affect treatment outcomes, its dynamic changes during therapy remain poorly characterized. Here, we used single-cell RNA sequencing and spatial transcriptomics data from patient-derived xenograft (PDX) models to investigate how the TME evolves under targeted treatment. We observed extensive microenvironmental remodeling throughout the course of therapy and these changes were found to be spatially organized. Notably, we identified spatially localized interactions between fibroblasts and macrophages with potential therapeutic relevance. Additionally, we found that TMEs in PDX models are largely conserved across cancer types and retain key features of endogenous TMEs, with variation by subtype and cell state. These findings offer new insights into the spatial and cellular dynamics of the TME during therapy and suggest avenues for improved treatment strategies.

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