Single-Cell and Bulk Transcriptomics Reveal a Cd8+ T-Cell Gene Signature Predicting Prognosis in Diffuse Large B-Cell Lymphoma Publisher Pubmed



Liu H ; Feng Y ; Qian Z ; Song Z ; Zhang N ; Yu J ; Liu X ; Qiu L ; Zhou S ; Gong W ; Meng B ; Abolhassani H ; Asghar M ; Li L Show All Authors
Source: Frontiers in Immunology Published:2025

Abstract

Background: Diffuse large B-cell lymphoma (DLBCL) exhibits immunological heterogeneity that influences outcomes of immunochemotherapy, with CD8+ T cells playing a critical role in patient prognosis. Methods: We integrated single-cell and bulk transcriptome data to establish a CD8⁺ T cell–associated prognostic signature. Single-cell RNA sequencing data from 29 samples (28 individuals), including DLBCL and reactive lymph nodes/tonsils, were analyzed to characterize CD8⁺ T cell heterogeneity, identify distinct subsets, and screen differentially expressed genes. Least absolute shrinkage and selection operator (LASSO) regression combined with multivariable Cox analysis was applied to bulk RNA-seq datasets to construct a prognostic model. Results: Analysis of 19,483 CD8⁺ T cells revealed eight transcriptionally distinct subsets, from which 48 genes were associated with clinical outcomes. Eight prognostic genes were incorporated into a CD8⁺ T cell–related signature, with higher CD69 and CD70 expression correlating with inferior survival. The signature effectively stratified patients into high- and low-risk groups that differed in cell-of-origin subtype, mutational landscape, and immune microenvironment characteristics. Moreover, the model showed potential to predict baseline response to chimeric antigen receptor T-cell (CAR-T) therapy. Conclusion: This study highlights CD8+ T cell heterogeneity in DLBCL and establishes a prognostic gene signature that informs patient survival prediction and CAR-T therapy efficacy. Copyright © 2025 Liu, Feng, Qian, Song, Zhang, Yu, Liu, Qiu, Zhou, Gong, Meng, Abolhassani, Asghar, Li, He, Zhang and Wang.