The First People's Hospital of Zunyi, Department of Hematology, The Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
The First People's Hospital of Zunyi, Department of Hematology, The Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
Leuk Res. 2024 Nov;146:107588. doi: 10.1016/j.leukres.2024.107588. Epub 2024 Sep 19.
Diffuse large B cell lymphoma (DLBCL) is a heterogeneous and aggressive B cell malignancy that accounts for about 30 % of non-Hodgkin lymphomas. The current standard treatment for DLBCL is rituximab plus chemotherapy, but many patients are refractory or relapse, indicating the need for improved understanding of its molecular pathology. T cell exhaustion is a state of dysfunction or impairment that occurs in chronic infections or cancers, and is associated with poor prognosis in DLBCL. However, the molecular mechanisms of T cell exhaustion in DLBCL are poorly understood. In this study, we performed a comprehensive analysis of T cell exhaustion in DLBCL using public single-cell transcriptome data. We identified different subtypes of T cells and characterized their gene expression features. We found that DLBCL had a significantly higher proportion of exhausted T cells than normal tonsil, and that exhausted T cells had distinct gene expression signatures from non-exhausted T cells. These signatures included genes related to inhibitory receptors, cytokines, transcription factors and metabolic enzymes. We also found that ID3 gene was significantly upregulated in exhausted T cells in DLBCL, which may play a key role in T cell exhaustion. We constructed a protein-protein interaction network, identifying major hub proteins involved in T cell exhaustion or migration. We also performed KEGG and GO enrichment analysis for the differentially expressed genes between exhausted and non-exhausted T cells, and found important signaling pathways related to T cell exhaustion in DLBCL. Our results provide new insights into the molecular mechanisms underlying T cell exhaustion and offer novel therapeutic targets for this complex disease.
弥漫性大 B 细胞淋巴瘤（DLBCL）是一种异质性和侵袭性的 B 细胞恶性肿瘤，约占非霍奇金淋巴瘤的 30%。目前，DLBCL 的标准治疗方法是利妥昔单抗联合化疗，但许多患者对此具有耐药性或复发，这表明需要更好地了解其分子病理学。T 细胞耗竭是一种在慢性感染或癌症中发生的功能障碍或损伤状态，与 DLBCL 的预后不良相关。然而，DLBCL 中 T 细胞耗竭的分子机制尚不清楚。在这项研究中，我们使用公共单细胞转录组数据对 DLBCL 中的 T 细胞耗竭进行了全面分析。我们鉴定了不同类型的 T 细胞，并描述了它们的基因表达特征。我们发现，DLBCL 中耗竭 T 细胞的比例明显高于正常扁桃体，并且耗竭 T 细胞与非耗竭 T 细胞具有明显不同的基因表达特征。这些特征包括与抑制性受体、细胞因子、转录因子和代谢酶相关的基因。我们还发现，ID3 基因在 DLBCL 中耗竭的 T 细胞中显著上调，这可能在 T 细胞耗竭中发挥关键作用。我们构建了一个蛋白质-蛋白质相互作用网络，确定了涉及 T 细胞耗竭或迁移的主要枢纽蛋白。我们还对耗竭和非耗竭 T 细胞之间的差异表达基因进行了 KEGG 和 GO 富集分析，发现了与 DLBCL 中 T 细胞耗竭相关的重要信号通路。我们的研究结果为 T 细胞耗竭的分子机制提供了新的见解，并为这一复杂疾病提供了新的治疗靶点。
