Control of the Immune Response by Pro-Angiogenic Factors
Open Access
- 2 April 2014
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Oncology
- Vol. 4, 70
- https://doi.org/10.3389/fonc.2014.00070
Abstract
The progressive conversion of normal cells into cancer cells is characterized by the acquisition of eight hallmarks. Among these criteria, the capability of the cancer cell to avoid the immune destruction is found. Thus, tumors develop mechanisms to become invisible to the immune system, such as the induction of immunosuppressive cells which are able to inhibit the development of an efficient immune response. Molecules produced in the tumor microenvironment are involved in the occurrence of an immunosuppressive microenvironment. Recently, it has been shown that Vascular Endothelial Growth Factor -A (VEGF-A) exhibits immunosuppressive properties in addition to its proangiogenic activities. VEGF-A can induce the accumulation of immature dendritic cells, myeloid derived suppressor cells, regulatory T cells and inhibit the migration of T lymphocytes to the tumor. Other proangiogenic factors such as Placental Growth Factor (PlGF) could also participate in tumor-induced immunosuppression, but only few works have been performed on this point. Here, we review the impact of proangiogenic factors (especially VEGF-A) on immune cells. Anti-angiogenic molecules, which target VEGF-A/VEGFR axis, have been developed in the last decades and are commonly used to treat cancer patients. These drugs have anti-angiogenic properties but can also counteract the tumor-induced immunosuppression. Based on these immunomodulatory properties, anti-angiogenic molecules could be efficiently associated with immunotherapeutic strategies in preclinical models. These combinations are currently under investigation in cancer patients.Keywords
This publication has 97 references indexed in Scilit:
- Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in CancerThe New England Journal of Medicine, 2012
- Consequence of dose scheduling of sunitinib on host immune response elements and vaccine combination therapyInternational Journal of Cancer, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Sunitinib facilitates the activation and recruitment of therapeutic anti‐tumor immunity in concert with specific vaccinationInternational Journal of Cancer, 2010
- Improved Survival with Ipilimumab in Patients with Metastatic MelanomaThe New England Journal of Medicine, 2010
- Sipuleucel-T Immunotherapy for Castration-Resistant Prostate CancerThe New England Journal of Medicine, 2010
- Influence of bevacizumab, sunitinib and sorafenib as single agents or in combination on the inhibitory effects of VEGF on human dendritic cell differentiation from monocytesBritish Journal of Cancer, 2009
- Regulation of immune responses by L-arginine metabolismNature Reviews Immunology, 2005
- The Hallmarks of CancerCell, 2000
- Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cellsNature Medicine, 1996