Immunity and immune suppression in human ovarian cancer

Abstract

Clinical outcomes in ovarian cancer are heterogeneous, independent of common features such as stage, response to therapy and grade. This disparity in outcomes warrants further exploration into tumor and host characteristics. One compelling issue is the response of the patient's immune system to her ovarian cancer. Several studies have confirmed a prominent role for the immune system in modifying disease course. This has led to the identification and evaluation of novel immune-modulating therapeutic approaches such as vaccination and antibody therapy. Antitumor immunity, however, is often negated by immune suppression mechanisms present in the tumor microenvironment. Thus, in the future, research into immunotherapy targeting ovarian cancer will probably become increasingly focused on combination approaches that simultaneously augment immunity while preventing local immune suppression. In this article, we summarize important immunological issues that could influence ovarian cancer outcome, including tumor antigens, endogenous immune responses, immune escape and new and developing immunotherapeutic strategies.

Figure 1. Immune microenvironment in ovarian cancer

Despite the presence of various immune effector cells (i.e., CD4 T cells, CD8 T cells and NK cells) that can attack the tumor, the presence of a complex immune suppressive network including Tregs, ImDCs and MDSCs along with their mediators (i.e., IL-10, TGF-β, B7-H1, PD-1 and arginase) effectively halts the antitumor immunity. DC: Dendritic cell; FR: Folate receptor; IGFBP: IGF binding protein; ImDC: Immature DC; MDSC: Myeloid-derived suppressor cell; PD: Programmed death.