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Single-cell and bulk transcriptomics reveal a CD8+ T-cell gene signature predicting prognosis in diffuse large B-cell lymphoma

Liu, Hengqi ; Feng, Yingfang ; Qian, Zhengzi ; Song, Zheng ; Zhang, Ning ; Yu, Jingwei ; Liu, Xia ; Qiu, Lihua ; Zhou, Shiyong and Gong, Wenchen , et al. (2025) In Frontiers in Immunology 16.
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.... (More)

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.

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type
Contribution to journal
publication status
published
subject
keywords
CD8+ T cells, chimeric antigenreceptor T cell therapy, diffuse large B-cell lymphoma, prognosis, single-cell RNA sequencing
in
Frontiers in Immunology
volume
16
article number
1685541
publisher
Frontiers Media S. A.
external identifiers
  • scopus:105026223074
  • pmid:41459519
ISSN
1664-3224
DOI
10.3389/fimmu.2025.1685541
language
English
LU publication?
yes
id
611d3620-8aaf-4976-bba1-fb36c224b283
date added to LUP
2026-02-23 09:57:26
date last changed
2026-09-09 13:41:15
@article{611d3620-8aaf-4976-bba1-fb36c224b283,
  abstract     = {{<p>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.</p>}},
  author       = {{Liu, Hengqi and Feng, Yingfang and Qian, Zhengzi and Song, Zheng and Zhang, Ning and Yu, Jingwei and Liu, Xia and Qiu, Lihua and Zhou, Shiyong and Gong, Wenchen and Meng, Bin and Abolhassani, Hassan and Asghar, Muhammad and Li, Lanfang and He, Jin and Zhang, Huilai and Wang, Xianhuo}},
  issn         = {{1664-3224}},
  keywords     = {{CD8+ T cells; chimeric antigenreceptor T cell therapy; diffuse large B-cell lymphoma; prognosis; single-cell RNA sequencing}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Immunology}},
  title        = {{Single-cell and bulk transcriptomics reveal a CD8<sup>+</sup> T-cell gene signature predicting prognosis in diffuse large B-cell lymphoma}},
  url          = {{http://dx.doi.org/10.3389/fimmu.2025.1685541}},
  doi          = {{10.3389/fimmu.2025.1685541}},
  volume       = {{16}},
  year         = {{2025}},
}