Influence of bevacizumab, sunitinib and sorafenib as single agents or in combination on the inhibitory effects of VEGF on human dendritic cell differentiation from monocytes

Autor: Lorena Erro, Natalia Suarez, Ignacio Melero, Sarai Solano, Alfonso Gurpide, Asis Palazon, Juan Dubrot, José María López-Picazo, Carlos Alfaro, E Grande-Pulido, Alvaro Gonzalez, Sandra Hervas-Stubbs, Jose Luis Perez-Gracia
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Vascular Endothelial Growth Factor A
Cancer Research
Indoles
Angiogenesis
Pyridines
sunitinib
T-Lymphocytes
Angiogenesis Inhibitors
Dendritic cell differentiation
Lymphocyte Activation
Dendritic cells
Tyrosine-kinase inhibitor
Monocytes
chemistry.chemical_compound
Sunitinib
Benzenesulfonates
Antibodies
Monoclonal
Cell Differentiation
Sorafenib
VEGF
Interleukin-12
Renal cell carcinoma
Kidney Neoplasms
Vascular endothelial growth factor
Bevacizumab
Vascular endothelial growth factor A
medicine.anatomical_structure
Oncology
medicine.drug
Niacinamide
medicine.medical_specialty
renal cell carcinoma
medicine.drug_class
Antineoplastic Agents
bevacizumab
Antibodies
Monoclonal
Humanized
Internal medicine
Cell Line
Tumor
medicine
Humans
Pyrroles
dendritic cells
Molecular Diagnostics
Carcinoma
Renal Cell
business.industry
Monocyte
Phenylurea Compounds
Dendritic cell
Endocrinology
chemistry
Cancer research
Lymphocyte Culture Test
Mixed
business
Zdroj: British Journal of Cancer
ISSN: 1532-1827
0007-0920
Popis: Vascular endothelial growth factor (VEGF) inhibits differentiation and maturation of dendritic cells (DC), suggesting a potential immunosuppressive role for this proangiogenic factor. Bevacizumab, sorafenib and sunitinib target VEGF-mediated angiogenesis and are active against several types of cancer, but their effects on the immune system are poorly understood. In this study, VEGF and supernatants of renal carcinoma cell lines cultured under hypoxia were found to alter the differentiation of human monocytes to DC. Resulting DC showed impaired activity, as assessed by the alloreactive mixed T-lymphocyte reaction. Bevacizumab and sorafenib, but not sunitinib, reversed the inhibitory effects of VEGF, but not of those mediated by tumour supernatants. Dendritic cells matured under the influence of VEGF expressed less human leukocyte antigen-DR (HLA-DR) and CD86, and this effect was restored by bevacizumab and sorafenib. Finally, tumour-cell supernatants decreased interleukin-12 (IL-12) production by mature DC, and such inhibition was not restored by any of the tested drugs, delivered either as single agents or in combination. The deleterious effects of tumour-cell supernatants were mainly mediated by thermostable molecules distinct from VEGF. These results indicate that inhibition of the differentiation of monocytes to DC is a multifactorial effect, and that they support the development of combinations of angiogenesis inhibitors with immunological modulators.
Databáze: OpenAIRE
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