The Web-Based Portal SpatialTME Integrates Histological Images with Single-Cell and Spatial Transcriptomics to Explore the Tumor Microenvironment

Abstract The tumor microenvironment (TME) represents a complex network in which tumor cells communicate not only with each other but also with stromal and immune cells. The intercellular interactions in the TME contribute to tumor initiation, progression, metastasis, and treatment outcome. Recent advances in spatial transcriptomics (ST) have revolutionized the molecular understanding of the TME at the spatial level. A comprehensive interactive analysis resource specifically designed for characterizing the spatial TME could facilitate further advances using ST. In this study, we collected 296 ST slides covering 19 cancer types and developed a computational pipeline to delineate the spatial structure along the malignant–boundary–nonmalignant axis. The pipeline identified differentially expressed genes and their functional enrichment, deconvoluted the cellular composition of the TME, reconstructed cell type–specific gene expression profiles at the sub-spot level, and performed cell–cell interaction analysis. Finally, the user-friendly database SpatialTME (http://www.spatialtme.yelab.site/) was constructed to provide search, visualization, and downloadable results. These detailed analyses are able to reveal the heterogeneous regulatory network of the spatial microenvironment and elucidate associations between spatial features and tumor development or response to therapy, offering a valuable resource to study the complex TME. Significance: SpatialTME provides spatial structure, cellular composition, expression, function, and cell–cell interaction information to enable investigations into the tumor microenvironment at the spatial level to advance understanding of cancer development and treatment.