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

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...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2017-03, Vol.77 (5), p.1097-1107
Main Authors: Manfroi, Benoit, McKee, Thomas, 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
Format: Article
Language:English
Subjects:
Acetylation
Animals
APRIL protein
B-cell lymphoma
Blood
Cancer
Chemokines
CXC chemokines
DNA methylation
Humans
Interleukin 8
Interleukin-8 - biosynthesis
Interleukin-8 - immunology
Leukocytes (neutrophilic)
Ligands
Lymphocytes B
Lymphoma
Lymphoma, Large B-Cell, Diffuse - genetics
Lymphoma, Large B-Cell, Diffuse - immunology
Lymphoma, Large B-Cell, Diffuse - metabolism
Lymphoma, Large B-Cell, Diffuse - pathology
Mice
Neutrophils
Neutrophils - immunology
Neutrophils - metabolism
Neutrophils - pathology
Tumor cells
Tumor Microenvironment - immunology
Tumor necrosis factor
Tumor Necrosis Factor Ligand Superfamily Member 13 - biosynthesis
Tumor Necrosis Factor Ligand Superfamily Member 13 - genetics
Tumor Necrosis Factor Ligand Superfamily Member 13 - immunology
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. .
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-16-0786