Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1038/sj.bjc.6604965

Type

Journal article

Journal

British journal of cancer

Publication Date

04/2009

Volume

100

Pages

1111 - 1119

Addresses

Gene Therapy and Hepatology Division, CIMA, Universidad de Navarra, Pamplona, Spain.

Keywords

Dendritic Cells, T-Lymphocytes, Monocytes, Cell Line, Tumor, Humans, Carcinoma, Renal Cell, Kidney Neoplasms, Benzenesulfonates, Phenylurea Compounds, Niacinamide, Pyridines, Pyrroles, Indoles, Angiogenesis Inhibitors, Vascular Endothelial Growth Factor A, Antineoplastic Agents, Interleukin-12, Antibodies, Monoclonal, Lymphocyte Culture Test, Mixed, Lymphocyte Activation, Cell Differentiation, Antibodies, Monoclonal, Humanized, Bevacizumab, Sorafenib, Sunitinib