基于肿瘤免疫微环境的弥漫大B细胞淋巴瘤预后分析  

Prognostic Analysis of Diffuse Large B-Cell Lymphoma Based on Tumor Immune Microenvironment

作　　者：黄玉洁 黄鑫[1] 郭宝平[1] 柯晴[1] 谭晓虹[1] 岑洪[1] Huang Yujie;Huang Xin;Guo Baoping;Ke Qing;Tan Xiaohong;Cen Hong(Department of Hematological Oncology,Guangxi Medical University Affiliated Tumor Hospital&Oncology Medical College Guangxi Cancer Institute&Tumor Hospital&Cancer Center,530021 Nanning,Guangxi,China)

机构地区：[1]广西医科大学附属肿瘤医院淋巴血液肿瘤科,南宁530021

出　　处：《肿瘤预防与治疗》2021年第2期108-116,共9页Journal of Cancer Control And Treatment

基　　金：广西自然科学基金项目重点项目(编号:2016GXNSFDA380029)。

摘　　要：目的:本研究探讨弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)免疫相关信号通路的活化及免疫细胞浸润模式,分析肿瘤免疫微环境与DLBCL预后的关系。方法:基于GEO数据库提取DLBCL相关数据集的基因表达数据,分析16条免疫相关信号通路富集水平及27种免疫细胞浸润水平与患者预后的关系,并比较ABC亚型和GCB亚型DLBCL通路富集水平和免疫细胞浸润水平的差异。结果:数据集生存分析结果显示,适应性免疫系统通路、淋巴细胞活化通路、MHC Ⅱ类抗原呈递信号通路、Ⅰ型干扰素信号通路、Ⅱ型干扰素信号通路、Th17细胞分化信号通路、T细胞受体信号通路以及细胞黏附信号通路富集分数高的患者预后较好,其中Ⅰ型干扰素信号通路在GCB亚型中显著富集。CD4+T淋巴细胞、CD4+效应记忆T细胞、CD4+记忆T细胞、CD8+T淋巴细胞、Th1细胞、活化树突状细胞在所有数据集中均表现为细胞浸润程度高者预后较好,嗜酸性粒细胞、M2型巨噬细胞、中性粒细胞、Th2细胞浸润程度高者则预后不良;中性粒细胞浸润程度在ABC亚型中显著高于GCB亚型。结论:DLBCL肿瘤微环境中的免疫细胞亚群和免疫相关信号通路与预后密切相关,此结果或可为将来基于免疫微环境的DLBCL分型提供理论基础。Objective:The purpose of this study was to investigate the activation of immune-related signaling pathway and the pattern of immune cell infiltration in diffuse large B-cell lymphoma(DLBCL),and analyze the relationship between tumor immune microenvironment and prognosis.Methods:Gene expression data in DLBCL-related datasets were obtained from the GEO database(GEO).Relations of the prognosis of patients to the enrichment level of 16 immune-related signal pathways and the infiltration level of 27 kinds of immune cells,respectively,were analyzed.And the differences in pathway enrichment level and immune cell infiltration level between the activated B-cell-like(ABC)subtype and the germinal center B-cell-like(GCB)subtype were compared.Results:The results of dataset-based survival analysis showed that patients'prognosis improved with the increase of enrichment scores of adaptive immune system signaling pathway,lymphocyte activation signaling pathway,MHC Class Ⅱ antigen presentation signaling pathway,TypeⅠInterferon signaling pathway,Type Ⅱ interferon signaling pathway,Th 17 cell differentiation signaling pathway,T Cell receptor signaling pathway and cell adhesion signaling pathway.The typeⅠinterferon signal pathway was significantly enriched in GCB subtypes.Patients with high infiltration levels of CD4+T-cells,CD4+Tem,CD4+memory Tcells,CD8+T-cells,Thl cells and aDC cells had a good prognosis,while those with high infiltration levels of eosinophils,M2 macrophages,neutrophils and Th2 cells had a poor prognosis.The infiltration degree of ABC subtype in neutrophils was significantly higher than that of GCB subtype.Conclusion:Immune cell subsets and immune-related signaling pathways in tumor microenvironment in DLBCL are closely related to prognosis.The results of this study provide a theoretical basis for future subtyping of DLBCL based on immune microenvironment.

关 键 词：弥漫大B细胞淋巴瘤 信号通路 免疫微环境 免疫细胞 预后 

分 类 号：R733.4[医药卫生—肿瘤]