ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Single-cell and Bulk Transcriptomics Reveal a CD8⁺ T-cell Gene Signature Predicting Prognosis in Diffuse Large B-cell Lymphoma
Provisionally accepted
Xianhuo Wang1*
Hengqi Liu1
Yingfang Feng1,2
Zhengzi Qian1Zheng Song1
Ning Zhang1Jingwei Yu1Xia Liu1Lihua Qiu1Shiyong Zhou1Wenchen Gong1Bin Meng1Lanfang Li1Jin He1Huilai Zhang1- 1Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
- 2The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
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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. Here, we developed a prognostic gene signature associated with tumor-infiltrating CD8+ T cells by integrating single-cell and bulk transcriptome data. Single-cell transcriptional profiles from 29 samples (28 individuals), including DLBCL and reactive lymph nodes/tonsils, encompassing 19,483 CD8+ T cells, revealed eight distinct CD8+ T cell populations and 48 differentially expressed genes linked to clinical outcomes. Using least absolute shrinkage and selection operator (LASSO) regression and multivariable Cox analysis, we identified eight genes significantly associated with prognosis and constructed a prognostic signature, with elevated CD69 and CD70 expression correlating with poor outcomes. Stratification of patients into high-and low-risk groups based on this signature revealed significant differences in cell of origin (COO) classification, gene mutations, and the tumor immune microenvironment, and the model also showed potential to predict chimeric antigen receptor T-cell (CAR-T) therapy response at baseline. 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.
Keywords: CD8+ T cells, single-cell RNA sequencing, prognosis, Chimeric antigenreceptor T cell therapy, Diffuse large B-cell lymphoma
Received: 14 Aug 2025; Accepted: 28 Nov 2025.
Copyright: © 2025 Wang, Liu, Feng, Qian, Song, Zhang, Yu, Liu, Qiu, Zhou, Gong, Meng, Li, He and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xianhuo Wang
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