Unveiling the role of spatial transcriptomics in the analysis of the tumor immune microenvironment (Review).

The tumor immune microenvironment plays a decisive role in tumor initiation, progression and therapeutic response. Spatial transcriptomics (ST) enables comprehensive analysis of the whole transcriptome or specific gene sets while preserving the original spatial location information within tissues, offering a revolutionary approach to unraveling the complexity of the tumor immune microenvironment in the spatial dimension. The present review aims to systematically elaborate on the role and application of ST in deciphering the tumor immune microenvironment. Focusing on tumor microenvironment niches at different stages of tumor progression, from precancerous lesions and locally advanced tumors to distant metastasis, recent advances in ST for mapping the spatial distribution and functional states of key cell subpopulations are summarized. The present review further highlights its potential for clinical translation in identifying spatially defined biomarkers and elucidating the mechanisms underlying therapeutic responses and analyze the key technical challenges that constrain the application of ST in clinical practice. In recent years, the rapid development of machine learning algorithms has provided new opportunities to overcome the technical limitations of ST. The deep integration of machine learning with ST is laying a solid theoretical foundation and technical support for precision medicine and early intervention.