학술논문
IL-8 Instructs Macrophage Identity in Lateral Ventricle Contacting Glioblastoma.
Document Type
Author
Medina S; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN, USA.; Brockman AA; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.; Cross CE; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN, USA.; Hayes MJ; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Mobley BC; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Mistry AM; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, TN, USA.; Chotai S; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, TN, USA.; Weaver KD; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, TN, USA.; Thompson RC; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, TN, USA.; Chambless LB; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, TN, USA.; Ihrie RA; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA.; Irish JM; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Source
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
Adult IDH-wildtype glioblastoma (GBM) is a highly aggressive brain tumor with no established immunotherapy or targeted therapy. Recently, CD32 + HLA-DR hi macrophages were shown to have displaced resident microglia in GBM tumors that contact the lateral ventricle stem cell niche. Since these lateral ventricle contacting GBM tumors have especially poor outcomes, identifying the origin and role of these CD32 + macrophages is likely critical to developing successful GBM immunotherapies. Here, we identify these CD32 + cells as M_IL-8 macrophages and establish that IL-8 is sufficient and necessary for tumor cells to instruct healthy macrophages into CD32 + M_IL-8 M2 macrophages. In ex vivo experiments with conditioned medium from primary human tumor cells, inhibitory antibodies to IL-8 blocked the generation of CD32 + M_IL-8 cells. Finally, using a set of 73 GBM tumors, IL-8 protein is shown to be present in GBM tumor cells in vivo and especially common in tumors contacting the lateral ventricle. These results provide a mechanistic origin for CD32 + macrophages that predominate in the microenvironment of the most aggressive GBM tumors. IL-8 and CD32 + macrophages should now be explored as targets in combination with GBM immunotherapies, especially for patients whose tumors present with radiographic contact with the ventricular-subventricular zone stem cell niche.
Competing Interests: Declaration of interests All authors declare no competing interests.
Competing Interests: Declaration of interests All authors declare no competing interests.