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Scientific article
English

CXCL-8/IL8 Produced by Diffuse Large B-cell Lymphomas Recruits Neutrophils Expressing a Proliferation-Inducing Ligand APRIL

Contributors

Manfroi, Benoit; Mckee, Thomas Alexander; Mayol, Jean Francois; Tabruyn, Sebastien; Moret, Sebastien; Villiers, Christian; Righini, Christian; Dyer, Martin; Callanan, Mary; Schneider, Pascal; Tzankov, Alexandar; Matthes, Thomas; Sturm, Nathalie; Huard, Bertrand

Published in

Cancer Research, vol. 77, no. 5, p. 1097-1107

Publication date

2017

Abstract

Tumor-infiltrating neutrophils have been implicated in malignant development and progression, but mechanisms are ill defined. Neutrophils produce a proliferation-inducing ligand APRIL/TNFSF13, a factor that promotes development of tumors from diverse origins, including diffuse large B-cell lymphoma (DLBCL). High APRIL expression in DLBCL correlates with reduced patient survival, but the pathway(s) dictating APRIL expression are not known. Here, we show that all blood neutrophils constitutively secrete APRIL, and inflammation-associated stimuli, such as TNF, further upregulate APRIL. In a significant fraction of DLBCL patients, tumor cells constitutively produced the ELC-CXC chemokine CXCL-8 (IL8), enabling them to recruit APRIL-producing blood neutrophils. CXCL-8 production in DLBCL was unrelated to the cell of origin, as APRIL-producing neutrophils infiltrated CXCL-8(+) DLBCL from both germinal center (GC) and non-GC subtypes. Rather, CXCL-8 production implied events affecting DNA methylation and acetylation. Overall, our results showed that chemokine-mediated recruitment of neutrophils secreting the tumor-promoting factor APRIL mediates DLBCL progression. Cancer Res; 77(5); 1097-107. ©2016 AACR.

Keywords

  • Animals
  • Humans
  • Interleukin-8/biosynthesis/immunology
  • Ligands
  • Lymphoma, Large B-Cell, Diffuse/genetics/immunology/metabolism/pathology
  • Mice
  • Neutrophils/immunology/metabolism/pathology
  • Tumor Microenvironment/immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 13/biosynthesis/genetics/immunology

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

MANFROI, Benoit et al. CXCL-8/IL8 Produced by Diffuse Large B-cell Lymphomas Recruits Neutrophils Expressing a Proliferation-Inducing Ligand APRIL. In: Cancer Research, 2017, vol. 77, n° 5, p. 1097–1107. doi: 10.1158/0008-5472.CAN-16-0786

Main files (1)

Article (Published version)

Identifiers

Journal ISSN

0008-5472
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Technical informations

Creation

16/11/2017 08:34:00

First validation

16/11/2017 08:34:00

Update

15/03/2023 02:21:51

Status update

15/03/2023 02:21:50

Last indexation

31/10/2024 08:36:01
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