观察对象:滤泡性淋巴瘤后的免疫微环境
Entourage: the immune microenvironment following follicular lymphoma
原文发布日期:2012-01-20
DOI: 10.1038/bcj.2011.53
类型: Original Article
开放获取: 是
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In follicular lymphoma, nonmalignant immune cells are important. Follicular lymphoma depends on CD4+ cells, but CD8+ cells counteract it. We hypothesized that the presence of follicular lymphoma is associated with higher CD4+ than CD8+ cell numbers in the tumor microenvironment but not in the immune system. Using flow cytometry, pre-treatment and follow-up CD4/CD8 ratios were estimated in the bone marrow, blood and lymph nodes of untreated follicular lymphoma patients in two independent data sets (N1=121; N2=166). The ratios were analyzed for their relation with bone marrow lymphoma involvement. Bone marrows were also investigated with immunohistochemistry. In either data set, the bone marrow CD4/CD8 ratios were higher in bone marrows involved with lymphoma (P=0.043 and 0.0002, respectively). The mean CD4/CD8 ratio was 1.0 in uninvolved and 1.4 in involved bone marrows. Also higher in involved bone marrows were CD4/CD56 and CD3CD25/CD3 ratios. No blood or lymph node ratios differed between bone marrow-negative and -positive patients. Sequential samples showed increased bone marrow CD4/CD8 ratios in all cases of progression to bone marrow involvement. Immunohistochemistry showed CD4+, CD57+, programmed death-1+, forkhead box protein 3+ and CD21+ cells accumulated inside the lymphoma infiltrates, whereas CD8+, CD56+ and CD68+ cells were outside the infiltrates. This study provides evidence in vivo that the microenvironment changes upon follicular lymphoma involvement.
在滤泡性淋巴瘤中,非恶性免疫细胞具有重要作用。滤泡性淋巴瘤依赖CD4+细胞,但CD8+细胞对其有抑制作用。我们假设滤泡性淋巴瘤的存在与肿瘤微环境中CD4+细胞数量高于CD8+细胞相关,但在免疫系统中并非如此。利用流式细胞术,在两个独立数据集(N1=121;N2=166)中,对未治疗的滤泡性淋巴瘤患者的骨髓、血液和淋巴结中的CD4/CD8比值进行了治疗前和随访期的评估。分析了这些比值与骨髓淋巴瘤受累的关系。骨髓还通过免疫组织化学进行了研究。在两个数据集中,受累骨髓的CD4/CD8比值均较高(P值分别为0.043和0.0002)。未受累骨髓的平均CD4/CD8比值为1.0,而受累骨髓为1.4。受累骨髓中CD4/CD56和CD3CD25/CD3比值也较高。骨髓阴性患者与阳性患者之间的血液或淋巴结比值无差异。连续样本显示,在所有进展为骨髓受累的病例中,骨髓CD4/CD8比值均增加。免疫组织化学显示,CD4+、CD57+、程序性死亡-1+、叉头框蛋白3+和CD21+细胞聚集在淋巴瘤浸润灶内,而CD8+、CD56+和CD68+细胞位于浸润灶外。本研究在体内提供了证据,表明滤泡性淋巴瘤受累时微环境会发生改变。
Entourage: the immune microenvironment following follicular lymphoma
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