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Archive > Volume 32 Issue 11 > 2025,32(11):1159-1168. DOI:10.3872/j.issn.1007-385X.2025.11.008 Prev Next
Clinical Research
Single-cell RNA sequencing unravels heterogeneity and prognostic significance of tumor-infiltrating B cells in colorectal cancer
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Abstract:
[Abstract] Objective: To characterize the heterogeneity of B cells in the colorectal cancer (CRC) tumor microenvironment (TME) through single-cell RNA sequencing (scRNA-seq), thereby providing a theoretical foundation for B cell-based prognostic assessment and immunotherapy. Methods: Fresh surgical specimens from patients with primary colorectal cancer (n = 36) were collected and subjected to scRNA-seq. Cell clustering was performed using Seurat (v5.0). Cell differentiation trajectories were analyzed with Monocle3 (v1.3) and scVelo (v0.3.0). Gene Set Enrichment Analysis (GSEA) was employed to identify relevant functional pathways, and the gene regulatory network was constructed using pySCENIC (v0.11.2). Results: 11 functional subtypes were identified from 24 652 B cells and 49 138 plasma cells. Pseudotime analysis revealed a differentiation trajectory of B cells from a naive to a tissue resident state. Stress-adapted B cells were enriched in tumor tissues (10.39%), exhibiting significant activation of the NOD-like receptor signaling pathway and antigen processing and presentation. Tissue-resident B cells accounted for 9.09% of tumor-infiltrating B cells and showed enhanced C-type lectin receptor signaling and endocytosis. Migratory B cells were least abundant in stage Ⅱ tumors (16.42%), with significant enrichment of metabolic pathways such as oxidative phosphorylation. Plasma cells were terminally differentiated, with IgG-type cells predominating in tumor tissues (20.68%). Conclusion: Stress-adapted and tissue-resident B cells may promote immune escape, while migratory B cells potentially exert anti-tumor effects. IgG-type plasma cells appear to be associated with immunosuppression.
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