Revisiting the immune microenvironment of human colorectal cancer in the era of single-cell and spatial omics

Colorectal cancer (CRC) remains a significant global health challenge, ranking among the leading causes of cancer-related morbidity and mortality. The tumor microenvironment (TME)—comprising immune cells, stromal elements, and extracellular matrix—plays a pivotal role in tumorigenesis, progression, and therapeutic resistance. Recent advancements in single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) have revolutionized our understanding of the CRC TME by allowing high-resolution profiling of cellular heterogeneity and spatial dynamics. These cutting-edge technologies have uncovered novel, previously uncharacterized subsets of immune and stromal cells, all of which significantly relate to immune evasion and malignant progression. This review consolidates recent insights from single-cell and spatial transcriptomic studies, emphasizing the identification of novel cellular subtypes and their roles in modulating the TME. We also discuss the therapeutic implications of these findings, particularly in the development of targeted immunotherapies and combinatorial strategies aimed at improving clinical outcomes for CRC patients. By deepening our understanding of this complex cellular ecosystem, these insights are expected to inform more precise and effective therapeutic approaches for CRC.