Background:Diffuse large B-cell lymphoma (DLBCL), the most common B-cell non-Hodgkin lymphoma, remains challenging because more than one-third of patients fail to achieve durable remission with frontline therapy; therefore, a systematic and comprehensive understanding of its underlying biology is essential to improve risk stratification and treatment outcomes.Methods:Based on 30 glycolysis-related genes selected from 72 candidates in the MSigDB database, we comprehensively evaluated glycolysis-related modification patterns in 562 DLBCL samples and analyzed their associations with immune cell infiltration and patient prognosis in the tumor microenvironment (TME). In vivo, we identified three immune subtypes in DLBCL mouse models and accessed their correlation with glycolytsis-related patterns and outcomes using histopathological evaluation (H&E) staining, Kaplan–Meier survival analysis, Western blotting, and immunohistochemistry.Results:Four distinct glycolysis modification patterns were identified, which correlated with three immune subtypes: immune-inflamed, immune-desert, and immune-excluded. The immune-inflamed subtype, characterized by prominent immune infiltration, was associated with favorable survival. In contrast, the immune-excluded subtype, defined by stromal activation, did not confer a survival advantage. The immune-desert subtype, marked by a lack of immune infiltration, was linked to poor survival outcomes. Finally, using the DLBCL mouse model, we validated these three immune subtypes and demonstrated their corresponding associations with glycolytic patterns and prognosis.Conclusions:Our work demonstrated that glycolysis-related modification patterns have correlations with the immune cell infiltration within the TME of DLBCL and that distinct glycolytic states are associated with different clinical outcomes. These findings provide a framework for improved prognostic stratification and may inform new therapeutic decision-making in DLBCL.
背景：弥漫性大B细胞淋巴瘤（DLBCL）作为最常见的B细胞非霍奇金淋巴瘤，其治疗仍面临挑战，超过三分之一的患者无法通过一线治疗获得持久缓解。因此，系统全面地理解其潜在生物学机制对于改善风险分层和治疗结果至关重要。 方法：基于从MSigDB数据库72个候选基因中筛选出的30个糖酵解相关基因，我们对562例DLBCL样本中的糖酵解相关修饰模式进行全面评估，并分析其与肿瘤微环境（TME）中免疫细胞浸润及患者预后的关联。通过组织病理学（H&E）染色、Kaplan-Meier生存分析、蛋白质印迹法和免疫组织化学技术，我们在DLBCL小鼠模型中鉴定出三种免疫亚型，并评估其与糖酵解相关模式及预后的相关性。 结果：研究识别出四种不同的糖酵解修饰模式，这些模式与三种免疫亚型相关：免疫炎症型、免疫荒漠型和免疫排斥型。以显著免疫浸润为特征的免疫炎症型与良好生存相关；而由基质活化定义的免疫排斥型未显示生存优势；缺乏免疫浸润的免疫荒漠型则与不良生存结局相关。最终通过DLBCL小鼠模型，我们验证了这三种免疫亚型，并证实其与糖酵解模式及预后的对应关联。 结论：本研究表明糖酵解相关修饰模式与DLBCL肿瘤微环境中的免疫细胞浸润存在相关性，且不同的糖酵解状态与差异化的临床结局相关。这些发现为改善DLBCL预后分层提供了理论框架，并可能为新的治疗决策提供依据。
肿瘤(癌症)患者之家