Fibromodulin as a novel tumor-associated antigen (TAA) in chronic lymphocytic leukemia (CLL), which allows expansion of specific CD8+ autologous T lymphocytes
Fibromodulin as a novel tumor-associated antigen (TAA) in chronic lymphocytic leukemia (CLL), which allows expansion of specific CD8+ autologous T lymphocytes
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DOI：
10.1182/blood-2004-04-1233
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发表时间：
2005-02-15
期刊：
影响因子：
20.3
通讯作者：
Wendtner, CM
中科院分区：
文献类型：
--
作者：
Mayr, C;Bund, D;Wendtner, CM
与正常B淋巴细胞相比，纤维调节素（FMOD）在慢性淋巴细胞白血病（CLL）细胞中高度过表达。因此，FMOD可能在CLL中作为潜在的肿瘤相关抗原（TAA），使FMOD特异性T细胞扩增。在来自16名不同患者的CLL样本中，通过实时逆转录聚合酶链反应（RT-PCR）检测到FMOD的高表达，与正常B淋巴细胞相比。我们使用非脉冲的天然CLL细胞和CD40配体（CD40L）刺激的CLL细胞作为抗原呈递细胞（APCs）扩增来自13名患者的自体T细胞。体外培养4周的T细胞数量增加了2- 3.5倍，识别HLA-A2二聚体结合的FMOD肽的T细胞数量增加了10倍。扩增后的T细胞也能够分泌干扰素- γ (ifn - γ)，这是干扰素- γ ELISPOT检测证实的抗原识别结果。T细胞不仅能识别hla - a2结合的FMOD肽，还能识别hla - a2限制性过表达的自体CLL细胞的FMOD。综上所述，FMOD首次在原代CLL细胞中被自然加工并以TAA的形式呈现，使自体肿瘤特异性T细胞得以扩增。(C) 2005年由美国血液病学会出版。
Fibromodulin (FMOD) was shown to be highly overexpressed in chronic lymphocytic leukemia (CLL) cells compared with normal B lymphocytes by gene expression profiling. Therefore FMOD might serve as potential tumor-associated antigen (TAA) in CLL, enabling expansion of FMOD-specific T cells. In CLL samples derived from 16 different patients, high expression of FMOD by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was detectable in contrast to normal B lymphocytes. We used unpulsed native CLL cells and CD40 ligand (CD40L)-stimulated CLL cells as antigen-presenting cells (APCs) to expand autologous T cells from 13 patients. The number of T cells during 4 weeks of in vitro culture increased 2- to 3.5-fold and the number of T cells recognizing FMOD peptides bound to HLA-A2 dimers increased 10-fold. The expanded T cells also were able to secrete interferon-gamma (IFN-gamma) upon recognition of the antigen demonstrated by IFN-gamma ELISPOT assays. T cells not only recognized HLA-A2-binding FMOD peptides presented by transporter-assocciated with antigen-processing (TAP)-deficient T2 cells, but also FMOD overexpressing autologous CLL cells in an HLA-A2-restricted manner. In summary, FMOD was shown for the first time to be naturally processed and presented as TAA in primary CLL cells, enabling the expansion of autologous tumor-specific T cells. (C) 2005 by The American Society of Hematology.