Neoplastic CD3⁺ B cells remodel the DLBCL tumor microenvironment via single-cell and spatial transcriptomics

This study constructs a high-resolution multi-omics map of Diffuse Large B-Cell Lymphoma (DLBCL) by integrating single-cell, single-nucleus, and spatial transcriptomics.

We identified a previously unrecognized, recurrent subset of malignant B cells that unexpectedly express CD3, a protein typically found only on T cells. This unusual CD3⁺ B cell population appears to be driven by a specific genetic circuit involving five key regulatory genes: BCLAF1, CHURC1, FLI1, NFATC2, and ELF2.

Spatial and functional analyses revealed that these cells are associated with macrophage enrichment and M2 polarization, potentially involving TGF-β signaling and contributing to an immunosuppressive tumor microenvironment. Clinically, the abundance of CD3⁺ B cells was associated with advanced disease stage, poor treatment response, and reduced survival.

Our findings support the presence of a CD3⁺ B cell subset with T cell-like features that is associated with tumor microenvironment remodeling and adverse clinical outcomes, highlighting molecular determinants like FLI1 and the TGF-β axis as potential therapeutic targets.