肿瘤细胞治疗研究
英文原题：Single-cell and bulk transcriptomics reveal a CD8(+) T-cell gene signature predicting prognosis in diffuse large B-cell lymphoma.
本研究突出了 DLBCL 中 CD8+ T 细胞的异质性，并建立了一个预后基因特征，可为患者生存预测和 CAR-T 治疗疗效提供信息。
背景：弥漫大B细胞淋巴瘤（DLBCL）存在免疫学异质性，会影响免疫化疗结局，其中CD8⁺ T细胞对患者预后至关重要。方法：整合单细胞和整体转录组数据，建立CD8 T细胞相关预后特征。分析来自29份样本（28名个体）的单细胞RNA测序数据，样本包括DLBCL及反应性淋巴结/扁桃体组织，用于描绘CD8 T细胞异质性、识别不同亚群并筛选差异表达基因。进一步结合最小绝对收缩与选择算子（LASSO）回归和多变量Cox分析，利用整体RNA测序数据集构建预后模型。结果：对19,483个CD8 T细胞的分析识别出8个转录特征不同的亚群，其中48个基因与临床结局相关。最终将8个预后基因纳入CD8 T细胞相关特征；CD69和CD70表达较高与生存较差相关。该特征可有效将患者分为高、低风险组，两组在细胞起源亚型、突变谱和免疫微环境特征方面存在差异。此外，该模型显示出预测CAR-T 细胞治疗基线应答的潜力。结论：本研究揭示DLBCL中CD8⁺ T细胞的异质性，并建立可用于预测患者生存及CAR-T疗效的预后基因特征。
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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