Neutrophil-derived APRIL concentrated in tumor lesions by proteoglycans correlates with human B-cell lymphoma aggressiveness
Neutrophil-derived APRIL concentrated in tumor lesions by proteoglycans correlates with human B-cell lymphoma aggressiveness
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DOI：
10.1182/blood-2006-02-001800
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发表时间：
2007-01-01
期刊：
影响因子：
20.3
通讯作者：
Huard, Bertrand
中科院分区：
文献类型：
--
作者：
Schwaller, Juerg;Schneider, Pascal;Huard, Bertrand
增殖诱导TNF配体（APRIL）共同刺激b细胞活化。当在小鼠中过度表达时，APRIL诱导b细胞肿瘤，使人想起b细胞慢性淋巴细胞白血病（B-CLL）。我们分析了APRIL在人类非霍奇金淋巴瘤中的原位表达。四月上调仅在高级别b细胞淋巴瘤、弥漫性大b细胞淋巴瘤（DLBCL）和伯基特淋巴瘤（BL）中观察到。在DLBCL和BL中分别有46%和20%的表达上调。在DLBCL中，中性粒细胞组成性地产生APRIL并浸润肿瘤组织，是APRIL的主要细胞来源。在罕见的DLBCL病例中，APRIL以组织细胞或间充质细胞为主。APRIL由中性粒细胞通过蛋白聚糖结合积聚在肿瘤细胞上分泌。除了蛋白聚糖外，DLBCL肿瘤细胞还表达APRIL信号受体TACI和/或BCMA，表明这些肿瘤细胞完全具备对APRIL的应答能力。一项回顾性临床分析显示，肿瘤病变中APRIL的高表达与患者总体生存率降低有显著相关性。因此，炎症细胞浸润淋巴瘤病变产生的APRIL可能增加肿瘤的侵袭性并影响疾病预后。(c) 2007年由美国血液学会出版
A PRoliferation-Inducing TNF Ligand (APRIL) costimulates B-cell activation. When overexpressed in mice, APRIL induces B-cell neoplasia, reminiscent of human B-cell chronic lymphoid leukemia (B-CLL). We analyzed APRIL expression in situ in human non-Hodgkin lymphomas. APRIL up-regulation was only observed in high-grade B-cell lymphomas, diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma (BL). Up-regulation was seen in 46% and 20% of DLBCL and BL, respectively. In DLBCL, neutrophils, constitutively producing APRIL and infiltrating the tumor tissue, were the main cellular source of APRIL. Rare DLBCL cases showed a predominance of histiocytes or mesenchymal cells as APRIL source. APRIL secreted by neutrophils accumulated on tumor cells via proteoglycan binding. In addition to proteoglycans, DLBCL tumor cells expressed the APRIL signaling receptor, TACI and/or BCMA, indicating that these tumor cells are fully equipped to respond to APRIL. A retrospective clinical analysis revealed a significant correlation between high expression of APRIL in tumor lesions and decreased overall patient survival rate. Hence, APRIL produced by inflammatory cells infiltrating lymphoma lesions may increase tumor aggressiveness and affect disease outcome. (c) 2007 by The American Society of Hematology