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Single-cell and bulk transcriptomics reveal a CD8+ T-cell gene signature predicting prognosis in diffuse large B-cell
Hengqi Liu1, Yingfang Feng1,2, Zhengzi Qian1
1State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine/Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, the Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China.
This study reveals CD8+ T cell heterogeneity in diffuse large B-cell lymphoma (DLBCL). A novel gene signature predicts patient survival and response to CAR-T therapy, improving prognostic accuracy.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- Diffuse large B-cell lymphoma (DLBCL) is immunologically heterogeneous, impacting treatment outcomes.
- CD8+ T cells are critical determinants of patient prognosis in DLBCL.
Purpose of the Study:
- To integrate single-cell and bulk transcriptome data to develop a prognostic signature based on CD8+ T cells in DLBCL.
- To characterize CD8+ T cell heterogeneity and identify key genes associated with clinical outcomes.
Main Methods:
- Single-cell RNA sequencing of 29 DLBCL and control samples to analyze CD8+ T cell subsets.
- LASSO regression and multivariable Cox analysis on bulk RNA-seq data to build a prognostic model.
- Identification of differentially expressed genes within CD8+ T cell subsets.
Main Results:
- Eight distinct CD8+ T cell subsets were identified, with 48 genes linked to clinical outcomes.
- A prognostic signature of eight genes was constructed; high CD69 and CD70 expression correlated with poorer survival.
- The signature stratified patients by subtype, mutational landscape, and immune microenvironment, and predicted CAR-T therapy response.
Conclusions:
- CD8+ T cell heterogeneity significantly impacts DLBCL prognosis.
- A novel CD8+ T cell-associated gene signature can predict survival and CAR-T therapy efficacy in DLBCL patients.
