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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
Authors: Alfaro, C. (Carlos)
Suarez, N. (Natalia)
Gonzalez, A. (Alvaro)
Solano, S. (Sarai)
Erro, L. (Lorena)
Dubrot, J. (Juan)
Palazon, A. (Asís)
Hervas-Stubbs, S. (Sandra)
Gurpide, A. (Alfonso)
Lopez-Picazo, J.M. (José M.)
Grande-Pulido, E. (E)
Melero, I. (Ignacio)
Perez-Gracia, J.L. (José Luis)
Keywords: Dendritic cells
Renal cell carcinoma
VEGF
Bevacizumab
Sunitinib
Sorafenib
Issue Date: 2009
Publisher: Cancer Research UK
Publisher version: http://www.nature.com/bjc/journal/v100/n7/full/6604965a.html
ISSN: 1532-1827
Citation: Alfaro C, Suarez N, Gonzalez A, Solano S, Erro L, Dubrot J, et al. 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. Br J Cancer 2009 Apr 7;100(7):1111-1119.
Abstract
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.
Permanent link: http://hdl.handle.net/10171/20368
Appears in Collections:DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista

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