StereoSiTE: a framework to spatially and quantitatively profile the cellular neighborhood organized iTME.

Background: Spatial transcriptome (ST) technologies are emerging as powerful tools for studying tumor biology. However, existing tools for analyzing ST data are limited, as they mainly rely on algorithms developed for single-cell RNA sequencing data and do not fully utilize the spatial information. While some algorithms have been developed for ST data, they are often designed for specific tasks, lacking a comprehensive analytical framework for leveraging spatial information.

Results: In this study, we present StereoSiTE, an analytical framework that combines open-source bioinformatics tools with custom algorithms to accurately infer the functional spatial cell interaction intensity (SCII) within the cellular neighborhood (CN) of interest. We applied StereoSiTE to decode ST datasets from xenograft models and found that the CN efficiently distinguished different cellular contexts, while the SCII analysis provided more precise insights into intercellular interactions by incorporating spatial information. By applying StereoSiTE to multiple samples, we successfully identified a CN region dominated by neutrophils, suggesting their potential role in remodeling the immune tumor microenvironment (iTME) after treatment. Moreover, the SCII analysis within the CN region revealed neutrophil-mediated communication, supported by pathway enrichment, transcription factor regulon activities, and protein-protein interactions.

Conclusions: StereoSiTE represents a promising framework for unraveling the mechanisms underlying treatment response within the iTME by leveraging CN-based tissue domain identification and SCII-inferred spatial intercellular interactions. The software is designed to be scalable, modular, and user-friendly, making it accessible to a wide range of researchers.