Spatial Analysis of the Tumor Microenvironment in Diffuse Large B-cell Lymphoma Reveals Clinically Relevant Cell Interactions and Recurrent Cellular Neighborhoods

Abstract

Recent studies have explored the composition of the tumor microenvironment (TME) in diffuse large B-cell lymphoma (DLBCL) However, cell-to-cell interactions, along with the spatial organization of DLBCL TME and their impact on patient outcomes, have remained poorly characterized. We applied multiplex immunofluorescence, cell phenotyping, and neighborhood analysis to investigate 1,218,756 single cells in 99 samples from patients with primary DLBCL. We identified 17 cell phenotypes and 10 recurrent cellular neighborhoods (RCN) across samples, subdividing DLBCLs into immune-poor areas and areas with diverse immune cell infiltrates. Avoidance of B cells and PD-1+ T cells was associated with less aggressive clinical characteristics and favorable survival. Likewise, the proximity of CD8+ T cell–rich and immune-poor RCNs translated to favorable patient outcomes, and the proximity of PD-L1+ B cell–rich and CD8+ T cell–rich RCNs to unfavorable patient outcomes. Our findings provide insights into the spatial interactions and organization of DLBCL TME with implications for patient outcomes.