SH3BP5-driven metabolic-immune crosstalk in DLBCL: a prognostic biomarker and therapeutic target for reshaping immunosuppressive microenvironment

作者：Tong Wu, Yi Yang, Yuan Zong, Jiawen Zhao, Xiaoyu Zhao, Lei Li, Yiming Gao, Ning Li, Liting Jiang, Yinyin Xie · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-06951-z · 被引用次数：2 · 研究领域：Lymphoma Diagnosis and Treatment、Cancer Immunotherapy and Biomarkers、CNS Lymphoma Diagnosis and Treatment

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous and aggressive hematologic malignancy, with the activated B-cell-like (ABC) subtype displaying particularly poor prognosis due to inherent treatment resistance and elevated recurrence rates. Despite advances in targeted therapies and immunotherapies, a significant proportion of patients experience relapse or refractory disease, highlighting the urgent need for novel biomarkers and innovative therapeutic strategies to improve clinical outcomes. METHODS: A multi-dimensional analysis of SH3BP5 expression was performed across DLBCL subtypes, integrating transcriptomic, proteomic, and clinical datasets to assess its correlation with immune infiltration, tumor metabolism, and patient prognosis. Single-cell RNA sequencing data were employed to examine the tumor microenvironment (TME) with higher resolution. Further analysis of the association between SH3BP5 and immune checkpoint gene expression was conducted to explore its potential role in immunotherapy response. Functional in vitro assays were carried out to assess the impact of SH3BP5 knockdown on DLBCL cell proliferation and apoptosis. RESULTS: The analysis revealed that SH3BP5 is preferentially overexpressed in the ABC subtype of DLBCL across multiple datasets and validated cohorts, and its high expression is significantly associated with poor overall survival. Single-cell transcriptomic profiling demonstrated that SH3BP5 is mainly expressed in malignan...