CXCL-8/IL-8 produced by diffuse large B-cell lymphomas recruits neutrophils expressing a proliferation inducing ligand APRIL
| Autor: | Mary Callanan, Martin J. S. Dyer, Alexandar Tzankov, Thomas Alexander Mckee, Pascal Schneider, Sebastien Moret, Bertrand Huard, Jean Francois Mayol, Nathalie Sturm, Christian Righini, Benoit Manfroi, Sébastien Tabruyn, Christian L. Villiers, Thomas Matthes |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Chemokine Neutrophils Tumor Necrosis Factor Ligand Superfamily Member 13 Lymphoma Large B-Cell Diffuse/genetics/immunology/metabolism/pathology Animals Humans Interleukin-8/biosynthesis Interleukin-8/immunology Ligands 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/immunology Neutrophils/metabolism Neutrophils/pathology Tumor Microenvironment/immunology Tumor Necrosis Factor Ligand Superfamily Member 13/biosynthesis Tumor Necrosis Factor Ligand Superfamily Member 13/genetics Tumor Necrosis Factor Ligand Superfamily Member 13/immunology Interleukin-8/biosynthesis/immunology 03 medical and health sciences 0302 clinical medicine Neutrophils/immunology/metabolism/pathology hemic and lymphatic diseases medicine Tumor Microenvironment Interleukin 8 B cell ddc:616 biology business.industry Interleukin-8 Germinal center Cancer medicine.disease Lymphoma 030104 developmental biology medicine.anatomical_structure Oncology Tumor Necrosis Factor Ligand Superfamily Member 13/biosynthesis/genetics/immunology Immunology DNA methylation biology.protein Tumor necrosis factor alpha Lymphoma Large B-Cell Diffuse business 030215 immunology |
| Zdroj: | Cancer Research Cancer research, vol. 77, no. 5, pp. 1097-1107 Cancer Research, Vol. 77, No 5 (2017) pp. 1097-1107 |
| ISSN: | 0008-5472 |
| DOI: | 10.1158/0008-5472.CAN-16-0786 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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