Single‐cell landscape and clinical outcomes of infiltrating B cells in colorectal cancer

Abstract B cells constitute a major component of infiltrating immune cells in colorectal cancer (CRC). However, the characteristics of B cells and their clinical significance remain unclear. In this study, using single‐cell RNA sequencing and multicolour immunofluorescence staining experiments, we identified five distinct subtypes of B cells with their marker genes, distribution patterns and functional properties in the CRC tumour microenvironment. Meanwhile, we found a higher proportion of IgG plasma cells in tumour sites than that in adjacent normal mucosal tissues. In addition, the CXCL13‐producing CD8 + T cells in the tumour tissues could promote the formation of tertiary lymphoid structure (TLS) B cells, and the CCL28–CCR10 axis is pivotal for IgG plasma cell migration from the periphery of TLSs to the tumour stroma. Finally, we identified four distinct colon immune classes (CICs: A–D) and found that CD20 + B cells within TLSs were enriched in one immune‐inflamed or hot tumour group (CIC D). This B cell‐rich group, which was characterized by strong antigen presentation, IgG plasma cells accumulation, microsatellite instability‐high (MSI‐H) and high tumour mutation burden (TMB‐H), as well as immunosuppressive property in particular, might become a potential predictive biomarker for future immunotherapy. Additionally, in an immunotherapy cohort, patients with the enrichment of B cells and TLSs were demonstrated to obtain significant therapeutic advantages. Together, our findings provide the detailed landscape of infiltrating B cells and their potential clinical significance in CRC.