Spatial omics of immunity: Mapping cellular landscapes in tissue microenvironments

The tumor microenvironment (TME) is composed of diverse heterogeneous components and plays a crucial role in immune cell infiltration, immune evasion, and dynamic interactions between tumor cells and the immune system. A precise understanding of the TME is essential for tissue immunology research and the development of effective immunotherapies. Technologies that spatially dissect the TME and analyze it at the molecular level are increasingly important. Recently, cutting-edge, high-resolution, high-multiplex molecular profiling technologies capable of high-throughput RNA and protein profiling while incorporating spatial information have been rapidly developing. This review describes a variety of cutting-edge spatial transcriptomics and proteomics technologies, including sequencing-based spatial transcriptomics, multiplex in situ hybridization imaging-based spatial proteomics, and multiomics, which are particularly useful for tissue immunology research. Technological advances in computational tools are discussed, as well as how researchers have interpreted visualized data using our own results as examples. These technologies enable simultaneous analysis of the diverse types and functional states of immune cells in cancer tissues within the tissue architecture, providing a crucial foundation for understanding immune cell organization, function, and cell-to-cell interactions of tissue immune responses. Current spatial molecular profiling technologies still face technological limitations in resolution and analytical complexity. The lack of data standardization across diverse platforms and experimental conditions remains a significant issue, hindering the reproducibility and comparability of research results. To overcome these limitations, multiomics integrated research combining spatial transcriptomics, proteomics, and genomics data is expected to become more active in the future, which will enable a more multidimensional understanding of the TME and tissue immune environment. The introduction of artificial intelligence and machine learning technologies is expected to enable more precise interpretation of the functional status and interactions of immune cells within organizations, ultimately contributing to the development of next-generation immunotherapies.