Spatially Resolved Transcriptomics: Revealing Tumor Microenvironment Heterogeneity to Advance Cancer Immunotherapy

Despite the availability of numerous approved immunotherapies for various cancers, durable progression-free survival remains relatively uncommon among patients with advanced cancer. As research into immunotherapy intensifies, the heterogeneity and complexity of the tumor microenvironment (TME) have emerged as critical determinants of treatment response and a major obstacle to understanding tumor resistance mechanisms. Recent advances in spatially resolved transcriptomics (SRT) enable transcriptome-wide measurement of gene expression while preserving essential spatial information, which supports the characterization of the features of the TME. This review outlines key challenges in cancer immunotherapy and emphasizes the importance of the TME in determining therapeutic efficacy. SRT strategies suitable is systematically introduced for TME profiling, comparing their relative advantages and limitations. Additionally, bioinformatics tools and methods used to reconstruct spatial tissue patterns are discussed from SRT data. Furthermore, how SRT is explored can enhance the understanding of the complexity and heterogeneity of the TME, facilitate the identification of novel therapeutic targets, and advance biomarker discovery to refine personalized treatment strategies for diverse cancer patients. Finally, future perspectives on the application of SRT in cancer immunotherapy and addressing the associated challenges are provided.