Spatial omics: Deciphering heterogeneity in the tumor immune microenvironment and resistance to immunotherapy

Drug resistance in tumor immunotherapy is a significant challenge, stemming from the high heterogeneity and intricate spatial architecture of the tumor immune microenvironment. Traditional omics technologies often fall short in elucidating this complexity due to the loss of spatial information. However, spatial omics technologies offer a solution by enabling multidimensional dissection of tumor ecosystems, capturing molecular expression profiles while preserving the native spatial architecture of tissues. This technological framework systematically uncovers the spatial essence of immune resistance through the integration of multimodal data, including spatial transcriptomics, proteomics, metabolomics, and epigenomics. It reveals that functional regions, formed by specific cell types at precise spatial locations through molecular interactions—including physical barriers, metabolic microenvironments, and immunosuppressive cellular networks—collectively drive immune exclusion and T-cell dysfunction. Beyond mere mechanistic exploration, spatial omics is driving a paradigm shift in clinical diagnosis and treatment, moving away from single-molecule biomarkers towards precision medicine based on spatial biomarkers. This provides novel blueprints for designing individualized combination therapeutic strategies. Despite challenges in technical standardization and clinical translation, the deep integration of multi-omics and artificial intelligence will empower spatial omics to usher tumor immunotherapy into a new era of "spatial precision."