title: CXCL-8/IL8 Produced by Diffuse Large B-cell Lymphomas Recruits Neutrophils Expressing a Proliferation-Inducing Ligand APRIL.
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.
authors.affiliation: Albert Bonniot Institute, INSERM U1209/University Grenoble-Alpes, La Tronche, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Manfroi
authors.affiliation: Clinical Pathology, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: McKee
authors.affiliation: Transcure Biosciences, Archamps Biopark, Archamps, France.
authors.forename: Jean Francois
authors.initials: JF
authors.lastname: Mayol
authors.affiliation: Transcure Biosciences, Archamps Biopark, Archamps, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Tabruyn
authors.affiliation: Department of Pathology-Immunology, Geneva University Medical Centre, Geneva, Switzerland.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Moret
authors.affiliation: Albert Bonniot Institute, INSERM U1209/University Grenoble-Alpes, La Tronche, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Villiers
authors.affiliation: Head and Neck Department, Grenoble University Hospital, La Tronche, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Righini
authors.affiliation: Ernest and Helen Scott Hematological Research Institute, University of Leicester, Leicester, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Dyer
authors.affiliation: Albert Bonniot Institute, INSERM U1209/University Grenoble-Alpes, La Tronche, France.
authors.forename: Mary
authors.initials: M
authors.lastname: Callanan
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Schneider
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Alexandar
authors.initials: A
authors.lastname: Tzankov
authors.affiliation: Hematology, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Matthes
authors.affiliation: Albert Bonniot Institute, INSERM U1209/University Grenoble-Alpes, La Tronche, France.|Department of Anatomy and Cytopathology, University Hospital of Grenoble, La Tronche, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sturm
authors.affiliation: Albert Bonniot Institute, INSERM U1209/University Grenoble-Alpes, La Tronche, France. bertrand.huard@univ-grenoble-alpes.fr.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Huard
mesh_terms: D000818:Animals; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000276:immunology; D008024:Ligands; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D059016:Tumor Microenvironment / Q000276:immunology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D008024:Ligands; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13