Mapping Myeloid Cell Diversity in Diffuse Large B-Cell Lymphoma: Impact on T Cell Exhaustion and Clinical Prognosis

Diffuse large B-cell lymphoma (DLBCL) is an aggressive subtype of B-cell lymphoma characterized by genetic variability and clinical heterogeneity. Single-cell sequencing technology enables mapping of intra-tumoral heterogeneity and microenvironment interactions. In this study, we analyzed single-cell and RNA expression microarray data from over 3,000 DLBCL patients to investigate the immune landscape of the tumor microenvironment and its association with clinical prognosis. Malignant B cells identified through B-cell receptor (BCR) clonal analysis and copy number variation (CNV) assessment exhibited enrichment in pathways related to the cell cycle, DNA replication and p53 signaling, which were closely related to adverse survival outcomes. Next, the myeloid cells derived from DLBCL tumor tissues could be further clustered into several distinct types, primarily comprising dendritic cells and macrophages. The increased prevalence of SPP1 ⁺ macrophages within the tumor microenvironment was correlated with inferior overall survival. Additionally, CellChat analysis revealed that frequent interactions between SPP1 ⁺ macrophages and CD8⁺ T cells may contribute to T cell exhaustion and create an immunosuppressive microenvironment. Collectively, the diverse sub-populations, particularly the immunosuppressive SPP1 ⁺ macrophages regulated immune suppression status within tumor microenvironment and represented a potential therapeutic target for DLBCL patients.