Carcinoma-Derived Interleukin-8 Disorients Dendritic Cell Migration Without Impairing T-Cell Stimulation

Autor: Elixabet Bolaños, Jose Luis Perez-Gracia, Carlos Alfaro, Sandra Hervas-Stubbs, Lorena Erro, Asis Palazon, Juan Dubrot, Ana Rouzaut, Alvaro Gonzalez, Ignacio Melero, Ivan Martinez-Forero, Alfonso Gurpide, Sarai Solano, Esperanza Feijoo, Natalia Suarez
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Chemokine
Neutrophils
T-Lymphocytes
lcsh:Medicine
Cell Movement/drug effects
Mice
SCID
Interleukin-8/pharmacology
Lymphocyte Activation
Mice
0302 clinical medicine
Cell Movement
Neoplasms
Basic Cancer Research
Dendritic Cells/pathology
Morphogenesis
Tumor Microenvironment
lcsh:Science
0303 health sciences
Multidisciplinary
T Cells
Lymphocyte Activation/drug effects
3. Good health
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Cytokines
Medicine
Neoplasms/metabolism
Research Article
T cell
Immune Cells
Immunology
Antigen-Presenting Cells
Cell Migration
Biology
Injections
Dendritic Cells/drug effects
03 medical and health sciences
HT29 Cells
Cell Line
Tumor
medicine
Cell Adhesion
Animals
Humans
Interleukin 8
Dendritic cell migration
030304 developmental biology
Immune Evasion
Cell Proliferation
Inflammation
Chemotactic Factors
lcsh:R
Interleukin-8
Immunity
T lymphocyte
Dendritic Cells
T-Lymphocytes/immunology
Xenograft Model Antitumor Assays
Cell culture
Immune System
Cancer research
biology.protein
lcsh:Q
Chemotaxis assay
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 6, Iss 3, p e17922 (2011)
Dadun. Depósito Académico Digital de la Universidad de Navarra
instname
PLoS ONE; Vol 6
ISSN: 1932-6203
Popis: BACKGROUND: Interleukin-8 (IL-8, CXCL8) is readily produced by human malignant cells. Dendritic cells (DC) both produce IL-8 and express the IL-8 functional receptors CXCR1 and CXCR2. Most human colon carcinomas produce IL-8. IL-8 importance in malignancies has been ascribed to angiogenesis promotion. PRINCIPAL FINDINGS: IL-8 effects on human monocyte-derived DC biology were explored upon DC exposure to recombinant IL-8 and with the help of an IL-8 neutralizing mAb. In vivo experiments were performed in immunodeficient mice xenografted with IL-8-producing human colon carcinomas and comparatively with cell lines that do not produce IL-8. Allogenic T lymphocyte stimulation by DC was explored under the influence of IL-8. DC and neutrophil chemotaxis were measured by transwell-migration assays. Sera from tumor-xenografted mice contained increasing concentrations of IL-8 as the tumors progress. IL-8 production by carcinoma cells can be modulated by low doses of cyclophosphamide at the transcription level. If human DC are injected into HT29 or CaCo2 xenografted tumors, DC are retained intratumorally in an IL-8-dependent fashion. However, IL-8 did not modify the ability of DC to stimulate T cells. Interestingly, pre-exposure of DC to IL-8 desensitizes such cells for IL-8-mediated in vitro or in vivo chemoattraction. Thereby DC become disoriented to subsequently follow IL-8 chemotactic gradients towards malignant or inflamed tissue. CONCLUSIONS: IL-8 as produced by carcinoma cells changes DC migration cues, without directly interfering with DC-mediated T-cell stimulation.
Databáze: OpenAIRE
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