A high proportion of bone marrow T cells with regulatory phenotype (CD4+CD25hiFoxP3+) in Ewing sarcoma patients is associated with metastatic disease
A high proportion of bone marrow T cells with regulatory phenotype (CD4+CD25hiFoxP3+) in Ewing sarcoma patients is associated with metastatic disease
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DOI：
10.1002/ijc.24461
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发表时间：
2009-08-15
影响因子：
6.4
通讯作者：
Rossig, Claudia
中科院分区：
文献类型：
--
作者：
Brinkrolf, Peter;Landmeier, Silke;Rossig, Claudia
免疫抑制性CD 4 + CD 25（hi）FoxP 3 + T细胞（T-reg细胞）在许多恶性肿瘤的肿瘤微环境中密度增加，并干扰保护性抗肿瘤免疫应答。骨尤因肉瘤（ES）被认为是来源于骨髓（BM）间充质细胞的起源，显微镜下骨髓受累定义了一个高复发风险的患者亚群。我们假设BM驻留的T细胞可能有助于ES免疫逃逸的环境。我们使用6色流式细胞术研究了包括NK细胞，78 T细胞，中枢和效应记忆CD 8+和CD 4 + T细胞以及具有调节表型的T细胞在诊断时从45名在标准化方案内治疗的原发性或复发性E患者获得的BM中的T-reg细胞。虽然复发患者的CD 4：CD 8 T细胞比例倒置，但CD 8+效应/记忆T细胞亚群和T-reg细胞与诊断时的患者无显著差异。未发现先天性和效应/记忆T细胞亚群与已知风险因素（包括年龄、性别、肿瘤部位、原发性转移和组织学肿瘤反应）的显著相关性。相比之下，与局限性ES相比，原发性转移性疾病患者中T-reg细胞的频率显著更高（5.0 vs. 3.3%，p = 0.01）。因此，转移性ES患者BM T-reg细胞的增加可能反映了有助于转移性疾病发展的免疫逃逸机制。免疫策略必须充分考虑尤文肿瘤免疫相互作用领域内的监管环境。(C)2009年UICC
Immunosuppressive CD4+CD25(hi)FoxP3+ T cells (T-reg cells) have been found at increased densities within the tumor microenvironment in many malignancies and interfere with protective antitumor immune responses. Osseous Ewing sarcomas (ESs) are thought to derive from a bone marrow (BM) mesenchymal cell of origin, and microscopic marrow involvement defines a subpopulation of patients at a high risk of relapse. We hypothesized that BM-resident T cells may contribute to a permissive milieu for immune escape of ESs. Using 6-color-flow cytometry, we investigated the pattern of immune cell subset distribution including NK cells, 78 T cells, central and effector memory CD8+ and CD4+ T cells as well as T cells with regulatory phenotype (T-reg cells) in BM obtained at diagnosis from 45 primary or relapsed E patients treated within standardized protocols. Although patients at relapse had an inverted CD4:CD8 T-cell ratio, neither CD8+ effector/memory T-cell subsets nor T-reg cells significantly differed from patients at diagnosis. No significant associations of innate and effector/memory T-cell subpopulations with known risk factors were found, including age, gender, tumor site, primary metastases and histological tumor response. By contrast, T-reg cells were found at significantly higher frequencies in patients with primary metastatic disease compared with localized ESs (5.0 vs. 3.3%, p = 0.01). Thus, increased BM T-reg cells in patients with metastasized ES may reflect an immune escape mechanism that contributes to the development of metastatic disease. Immunotherapeutic strategies will have to adequately consider the regulatory milieu within areas of Ewing tumor-immune interactions. (C) 2009 UICC