CXCR1 and CXCR2 chemokine receptor agonists produced by tumors induce neutrophil extracellular traps that interfere with immune cytotoxicity
Keywords: 
Immune checkpoint blockade
Neutrophil extracellular traps
Tumor-associated neutrophils
Issue Date: 
2020
Publisher: 
Elsevier
Project: 
info:eu-repo/grantAgreement/AEI/Retos Investigación: Proyectos I+D+i/SAF2017-83267-C2-1-R/ES/ADMINISTRACION INTRATUMORAL Y DIANIZADA DE AGENTES DE INMUNOTERAPIA PARA EL TRATAMIENTO DEL CANCER
635122 - PROCROP - Professional cross-priming for ovary and prostate cancer
ISSN: 
1097-4180
Note: 
All rights are reserved, including those for text and data mining, AI training, and similar technologies. For all open access content, the Creative Commons licensing terms apply.
Citation: 
Teijeira, A. (Álvaro); Garasa, S. (Saray); Gato-Cañas, M. (María); et al. "CXCR1 and CXCR2 chemokine receptor agonists produced by tumors induce neutrophil extracellular traps that interfere with immune cytotoxicity". Immunity. 52 (5), 2020, 856 - 871
Abstract
Neutrophils are expanded and abundant in cancer-bearing hosts. Under the influence of CXCR1 and CXCR2 chemokine receptor agonists and other chemotactic factors produced by tumors, neutrophils, and granulocytic myeloid-derived suppressor cells (MDSCs) from cancer patients extrude their neutrophil extracellular traps (NETs). In our hands, CXCR1 and CXCR2 agonists proved to be the major mediators of cancer-promoted NETosis. NETs wrap and coat tumor cells and shield them from cytotoxicity, as mediated by CD8+ T cells and natural killer (NK) cells, by obstructing contact between immune cells and the surrounding target cells. Tumor cells protected from cytotoxicity by NETs underlie successful cancer metastases in mice and the immunotherapeutic synergy of protein arginine deiminase 4 (PAD4) inhibitors, which curtail NETosis with immune checkpoint inhibitors. Intravital microscopy provides evidence of neutrophil NETs interfering cytolytic cytotoxic T lymphocytes (CTLs) and NK cell contacts with tumor cells.

Files in This Item:
Thumbnail
File
1-s2.0-S1074761320300893-main.pdf
Description
Size
8.4 MB
Format
Adobe PDF


Statistics and impact
0 citas en
0 citas en

Items in Dadun are protected by copyright, with all rights reserved, unless otherwise indicated.