Enrichment of functional CD8 memory T cells specific for MUC1 in bone marrow of patients with multiple myeloma

Enrichment of functional CD8 memory T cells specific for MUC1 in bone marrow of patients with multiple myeloma
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DOI:
10.1182/blood-2004-01-0366
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发表时间:
2005-03-01
期刊:
影响因子:
20.3
通讯作者:
Beckhove, P
Beckhove, P
中科院分区:
医学1区
文献类型:
--
作者:
Choi, C;Witzens, M;Beckhove, P

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多发性骨髓瘤(MM)是最常见的血液系统恶性肿瘤之一。尽管有广泛的治疗方法,治愈仍然是罕见的例外。未来免疫治疗的一个重要问题是表征适当的肿瘤相关抗原。最近,在大多数多发性骨髓瘤细胞系上检测到高度糖基化的粘蛋白MUC 1。我们分析了68例HLA-A2阳性骨髓瘤患者的骨髓和外周血中MUC 1衍生肽LLLLTVLTV特异性CD 8 T细胞的存在和功能活性。与健康供体的相应样本相比,44%的MM患者的外周血(PB)或骨髓(BM)新鲜分离样本中MUC 1特异性CD 8 T细胞的频率升高。BM驻留的T细胞具有更高的功能能力比PB衍生的T细胞的干扰素γ(IFN-γ)的分泌,穿孔素的生产,和细胞毒性的特异性再活化。(C)2005年美国血液学会
Multiple myeloma (MM) is one of the most common hematologic malignancies. Despite extensive therapeutical approaches, cures remain rare exceptions. An important issue for future immunologic treatments is the characterization of appropriate tumor-associated antigens. Recently, a highly glycosylated mucin MUC1 was detected on a majority of multiple myeloma cell lines. We analyzed bone marrow and peripheral blood of 68 patients with HLA-A2-positive myeloma for the presence and functional activity of CD8 T cells specific for the MUC1-derived peptide LLLLTVLTV. Forty-four percent of the patients with MM contained elevated frequencies of MUC1-specific CD8 T cells in freshly isolated samples from peripheral blood (PB) or bone marrow (BM) compared with corresponding samples from healthy donors. BM-residing T cells possessed a higher functional capacity upon specific reactivation than PB-derived T cells with regard to interferon gamma (IFN-gamma) secretion, perforin production, and cytotoxicity. (C) 2005 by The American Society of Hematology