Exploring the Immunological Mechanisms Underlying the Anti-vascular Endothelial Growth Factor Activity in Tumors

Abstract

Several studies report the key role of the vascular endothelial growth factor (VEGF) signaling on angiogenesis and on tumor growth. This has led to the development of a number of VEGF-targeted agents to treat cancer patients by disrupting the tumor blood vessel supply. Of them, bevacizumab, an FDA-approved humanized monoclonal antibody against VEGF, is the most promising. Although the use of antibodies targeting the VEGF pathway has shown clinical benefits associated with a reduction in the tumor blood vessel density, the inhibition of VEGF-driven vascular effects is only part of the functional mechanism of these therapeutic agents in the tumor ecosystem. Compelling reports have demonstrated that VEGF confers, in addition to the activation of angiogenesis-related processes, immunosuppressive properties in tumors. It is also known that structural remodeling of the tumor blood vessel bed by anti-VEGF approaches affect the influx and activation of immune cells into tumors, which might influence the therapeutic results. Besides that, part of the therapeutic effects of antiangiogenic antibodies, including their role in the tumor vascular network, might be triggered by Fc receptors in an antigen-independent manner. In this mini-review, we explore the role of VEGF inhibitors in the tumor microenvironment with focus on the immune system, discussing around the functional contribution of both bevacizumab's Fab and Fc domains to the therapeutic results and the combination of bevacizumab therapy with other immune-stimulatory settings, including adjuvant-based vaccine approaches.

Opposite Macrophage Polarization in Different Subsets of Ovarian Cancer: Observation from a Pilot Study

“…Furthermore, the data on bevacizumab have to be considered with this in mind. Anti-VEGF therapy, which was proven beneficial in ovarian cancer [20], is indeed known to modify the immune contexture [37] and is expected to reduce the amount of M2 macrophages. On the other hand, there is evidence that the presence of M2 macrophages can be an indication of resistance to anti-VEGF therapy [22,38,39].…”

TCR Redirected T Cells for Cancer Treatment: Achievements, Hurdles, and Goals

“…This process is largely orchestrated by the vascular-endothelial growth factor (VEGF) and results in tumor growth promotion and altered inflammation ( 303 ). VEGF inhibitors are currently used in the treatment of several cancers ( 304 ) owing, in particular, to their ability to increase T cell tumor homing ( 305 – 309 ). By promoting vessel maturation, VEGF inhibitors positively impact on immunotherapy and ACT ( 310 ).…”

Tackling Resistance to Cancer Immunotherapy: What Do We Know?

“…Furthermore, vascular endothelial growth factor (VEGF) secreted by tumor cells can also act to impede T cell recruitment [ 33 ]. Administration of anti VEGF that somehow normalized the vasculature has been found to significantly increase T cell recruitment into the tumor microenvironment [ 33 ]. Once recruited into tumor microenvironment, the T cells need to cross react with tumor antigens through the antigen presentation process.…”