Reshaping the colorectal cancer immune microenvironment: insights from 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. Accumulating evidence indicates that disease progression and therapeutic resistance in CRC are not solely tumor cells but are critically shaped by the tumor microenvironment (TME), including immune and stromal compartments and the extracellular matrix. Recent advances in single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) have enabled the integration of cellular identity with spatial context, thereby defining spatial niches and interaction networks that modulate both antitumor immunity and tumor-promoting programs in CRC. This review synthesizes scRNA-seq and spatial transcriptomic studies of CRC to characterize cellular heterogeneity and to delineate spatial niche organization and functional crosstalk within the TME. Building on these insights, we summarize emerging therapeutic perspectives in CRC, including rational combination immunotherapy strategies and promising targets such as SPP1⁺ tumor-associated macrophages.