Carcinoma-derived interleukin-8 disorients dendritic cell migration without impairing T-cell stimulation

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 promotio...

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Autores: Alfaro, C. (Carlos)|||/items/6543acf2-b8b2-46cc-b8ed-884af7fcf8bd, Suarez, N. (Natalia)|||/items/cd432081-6202-4ad4-9acf-af1ea2dac674, Martinez-Forero, I. (Iván)|||/items/21907c09-a679-4879-af20-10949920607d, Palazon, A. (Asís)|||/items/aad3d021-ca2e-4de3-851a-9ee07f77d05e, Rouzaut, A. (Ana)|||/items/4cb4f93a-048e-4093-a125-f987ff4b9024, Solano, S. (Sarai)|||/items/a1ec3052-3857-4856-917e-eb920d47c4d7, Feijoo-Blanco, E. (Esperanza)|||/items/a4066dcd-ee21-4cb4-8eb0-1fa574e501b0, Gurpide-Ayarra, L.A. (Luis Alfonso)|||/items/0935e09d-b036-414b-ac0f-688dbfa94d7f, Bolaños-Mateo, E. (Elixabet)|||/items/073a1977-5579-4bd1-8604-98b3ccfd4361, Erro, L. (Lorena)|||/items/6ce411ec-7817-482e-8ea4-3c00fac41ed3, Dubrot-Armendáriz, J. (Juan)|||/items/b42afe78-7095-4682-8c2c-0904580d8d53, Hervas-Stubbs, S. (Sandra)|||/items/8f56cb52-4465-4428-8acf-e50439c6be8f, Gonzalez-Hernandez, Á. (Álvaro)|||/items/901d58bd-7116-4c53-ae90-206bbc0afbd3, Perez-Gracia, J.L. (Jose Luis)|||/items/7be82c5d-4858-4e04-bd77-7ef5a883021b, Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4e
Tipo de recurso: artículo
Fecha de publicación:2011
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/20286
Acceso en línea:https://hdl.handle.net/10171/20286
Access Level:acceso abierto
Palabra clave:Cell Movement/drug effects
Dendritic Cells/drug effects
Dendritic Cells/pathology
Interleukin-8/pharmacology
Lymphocyte Activation/drug effects
Neoplasms/metabolism
T-Lymphocytes/immunology
Área de Terapia Celular
Descripción
Sumario: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.

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