Tumor immune surveillance and ovarian cancer

Abstract

In the past few years, cancer immunotherapies have produced promising results. Although traditionally considered unresponsive to immune therapy, increasing evidence indicates that ovarian cancers are, in fact, immunogenic tumors. This evidence comes from diverse epidemiologic and clinical data comprising evidence of spontaneous antitumor immune response and its association with longer survival in a proportion of ovarian cancer patients; evidence of tumor immune evasion mechanisms and their association with short survival in some ovarian cancer patients; and finally pilot data supporting the efficacy of immune therapy. Below we will discuss lessons learned on the biology underlying ovarian cancer immune rejection or tolerance and we will discuss its association with clinical outcome. We will discuss the role of angiogenesis and the tumor endothelium on regulation of the antitumor immune response with a special emphasis on the role of vascular endothelial growth factor (VEGF) in the suppression of immunological processes, which control tumor progression and its unique crosstalk with endothelin systems, and how their interactions may shape the antitumor immune response. In addition, we will discuss mechanisms of tumor tolerance through the suppression or exhaustion of effector cells and how these could be countered in the clinic. We believe that understanding these pathways in the tumor microenvironment will lead to novel strategies for enhancing ovarian cancer immunotherapy.

Bevacizumab plus Ipilimumab in Patients with Metastatic Melanoma

“…Specifically, the concentration of CD31 staining at the interendothelial junctions of bevacizumab plus ipilimumab treated specimens indicates vessels adapted for efficient lymphocyte trafficking ( 19 ). These results are consistent with previous observations of anti-VEGF treatment increasing lymphocyte tumor infiltrates in adoptive therapy models ( 20 , 21 ).…”

Deciphering and Reversing Tumor Immune Suppression

“…The molecular basis of immune escape in these tumors may be downregulation of the antigen presenting machinery in tumor cells, which may be due to epigenetic deregulation, and can be reversed with histone deacetylase inhibitors (Magner et al, 2000) or the use of low-dose IFNγ (Propper et al, 2003). Alternatively, a prohibitive tumor endothelial barrier may be the reason why T cells may not be able to home to tumors (Kandalaft et al, 2011). Proangiogenic signals can deregulate adhesive properties of the tumor endothelium and thus antiangiogenesis therapy could be contributory to activate antitumor immune response (Motz and Coukos, 2011).…”

Dual Blockade of PD-1 and CTLA-4 Combined with Tumor Vaccine Effectively Restores T-Cell Rejection Function in Tumors

“…Mechanisms regulating immune activation in cancer progression have been extensively investigated (4–16). There are multiple inhibitory mechanisms that suppress immune responses, including inhibitory receptors, secreted soluble inhibitors (IL-10 and TGF-β), and regulatory T cells (Tregs) (3, 16–17, 19–22). However, how these factors interact with each other in the tumor environment needs further study.…”