Neutrophil-derived APRIL concentrated in tumor lesions by proteoglycans correlates with human B-cell lymphoma aggressiveness

被引：126

作者：

Schwaller, Juerg

Schneider, Pascal

Mhawech-Fauceglia, Paulette

McKee, Thomas

Myit, Samir

Matthes, Thomas

Tschopp, Jurg

Donze, Olivier

Le Gal, Frederique-Anne

Huard, Bertrand

机构：

[1] Univ Geneva, Med Ctr, Dept Pathol, Louis Jeantet Lab, CH-1211 Geneva 4, Switzerland

[2] Univ Lausanne, Dept Biochem, CH-1015 Lausanne, Switzerland

[3] Roswell Pk Canc Inst, Buffalo, NY 14263 USA

[4] Univ Hosp Geneva, Dept Internal Med, Hematol Unit, Geneva, Switzerland

[5] Apotech Corp, Epalinges, Switzerland

[6] Univ Hosp Geneva, Dept Dermatol, Geneva, Switzerland

[7] Univ Geneva, Med Ctr, Louis Jeantet Lab, CH-1211 Geneva, Switzerland

[8] Univ Hosp Geneva, Dept Dermatol, Geneva, Switzerland

[9] Univ Hosp Geneva, Dept Pathol Immunol, Geneva, Switzerland

[10] Univ Basel Hosp, Dept Res, CH-4031 Basel, Switzerland

来源：

BLOOD | 2007年 / 109卷 / 01期

关键词：

D O I：

10.1182/blood-2006-02-001800

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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

引用

页码：331 / 338

页数：8

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