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

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

doi:10.1158/0008-5472.CAN-16-0786

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Title		CXCL-8/IL8 Produced by Diffuse Large B-cell Lymphomas Recruits Neutrophils Expressing a Proliferation-Inducing Ligand APRIL.
Authors		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 show all authors [1 - 14]
Published in		Cancer Research. 2017, vol. 77, no. 5, p. 1097-1107
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
Identifiers		DOI: 10.1158/0008-5472.CAN-16-0786 PMID: 27923834
Full text		Article (Published version) (1.6 MB) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine
Research groups		Analyses cellulaires et moléculaires des hémopathies malignes (929) Lymphomes MALT et réplication virale (807)
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 https://archive-ouverte.unige.ch/unige:99094