单细胞和空间转录组学揭示了弥漫性大B细胞淋巴瘤中一个与预后不良和免疫微环境耗竭相关的高糖酵解B细胞和肿瘤相关巨噬细胞簇。
Single-cell and spatial transcriptomics reveal a high glycolysis B cell and tumor-associated macrophages cluster correlated with poor prognosis and exhausted immune microenvironment in diffuse large B-cell lymphoma.
作者信息
Dai Liyuan, Fan Guangyu, Xie Tongji, Li Lin, Tang Le, Chen Haizhu, Shi Yuankai, Han Xiaohong
机构信息
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.
出版信息
Biomark Res. 2024 Jun 5;12(1):58. doi: 10.1186/s40364-024-00605-w.
BACKGROUND
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous malignancy characterized by varied responses to treatment and prognoses. Understanding the metabolic characteristics driving DLBCL progression is crucial for developing personalized therapies.
METHODS
This study utilized multiple omics technologies including single-cell transcriptomics (n = 5), bulk transcriptomics (n = 966), spatial transcriptomics (n = 10), immunohistochemistry (n = 34), multiple immunofluorescence (n = 20) and to elucidate the metabolic features of highly malignant DLBCL cells and tumor-associated macrophages (TAMs), along with their associated tumor microenvironment. Metabolic pathway analysis facilitated by scMetabolism, and integrated analysis via hdWGCNA, identified glycolysis genes correlating with malignancy, and the prognostic value of glycolysis genes (STMN1, ENO1, PKM, and CDK1) and TAMs were verified.
RESULTS
High-glycolysis malignant DLBCL tissues exhibited an immunosuppressive microenvironment characterized by abundant IFN_TAMs (CD68CXCL10PD-L1) and diminished CD8 T cell infiltration. Glycolysis genes were positively correlated with malignancy degree. IFN_TAMs exhibited high glycolysis activity and closely communicating with high-malignancy DLBCL cells identified within datasets. The glycolysis score, evaluated by seven genes, emerged as an independent prognostic factor (HR = 1.796, 95% CI: 1.077-2.995, p = 0.025 and HR = 2.631, 95% CI: 1.207-5.735, p = 0.015) along with IFN_TAMs were positively correlated with poor survival (p < 0.05) in DLBCL. Immunohistochemical validation of glycolysis markers (STMN1, ENO1, PKM, and CDK1) and multiple immunofluorescence validation of IFN_TAMs underscored their prognostic value (p < 0.05) in DLBCL.
CONCLUSIONS
This study underscores the significance of glycolysis in tumor progression and modulation of the immune microenvironment. The identified glycolysis genes and IFN_TAMs represent potential prognostic markers and therapeutic targets in DLBCL.
背景
弥漫性大B细胞淋巴瘤（DLBCL）是一种异质性恶性肿瘤，其对治疗的反应和预后各不相同。了解驱动DLBCL进展的代谢特征对于开发个性化治疗至关重要。
方法
本研究利用了多种组学技术，包括单细胞转录组学（n = 5）、批量转录组学（n = 966）、空间转录组学（n = 10）、免疫组织化学（n = 34）、多重免疫荧光（n = 20），以阐明高恶性DLBCL细胞和肿瘤相关巨噬细胞（TAM）的代谢特征及其相关的肿瘤微环境。通过scMetabolism促进的代谢途径分析以及通过hdWGCNA进行的综合分析，确定了与恶性程度相关的糖酵解基因，并验证了糖酵解基因（STMN1、ENO1、PKM和CDK1）和TAM的预后价值。
结果
高糖酵解恶性DLBCL组织表现出免疫抑制微环境，其特征是大量IFN_TAM（CD68CXCL10PD-L1）且CD8 T细胞浸润减少。糖酵解基因与恶性程度呈正相关。IFN_TAM表现出高糖酵解活性，并与数据集中鉴定出的高恶性DLBCL细胞密切通信。由七个基因评估的糖酵解评分成为独立的预后因素（HR = 1.796，95%CI：1.077 - 2.995，p = 0.025；HR = 2.631，95%CI：1.207 - 5.735，p = 0.015），并且IFN_TAM与DLBCL患者的不良生存呈正相关（p < 0.05）。糖酵解标志物（STMN1、ENO1、PKM和CDK1）的免疫组织化学验证以及IFN_TAM的多重免疫荧光验证强调了它们在DLBCL中的预后价值（p < 0.05）。
结论
本研究强调了糖酵解在肿瘤进展和免疫微环境调节中的重要性。鉴定出的糖酵解基因和IFN_TAM代表了DLBCL中潜在的预后标志物和治疗靶点。
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