Indoleamine 2,3-dioxygenase and immune tolerance in ovarian cancer

Ovarian cancer is the leading cause of cancer death among gynecologic malignancies despite significant advances in cytoreductive surgery and chemotherapy, and novel therapeutic approaches are urgently needed. Immunotherapy is one of these strategies; however, its clinical applications have shown limited efficacy. This may be attributed to tumor-induced immune tolerance, and much attention has been paid to overcoming these immune resistance mechanisms. This review focuses on the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) and shows the role of IDO and its clinical potential in ovarian cancer.

IDO suppresses the proliferation of effector T cells or natural killer cells and their killer functions. In ovarian cancer, high IDO expression in tumor cells was correlated with a reduced number of tumor-infiltrating lymphocytes. The IDO expression was also correlated with advanced surgical stage and impaired survival. Preclinical studies in mice demonstrated that oral administration of IDO inhibitors suppressed peritoneal dissemination and potentiated the antitumor efficacy of chemotherapeutic agents.

IDO induces immune tolerance and promotes ovarian cancer progression. Tumoral IDO expression is correlated with impaired clinical outcome. IDO inhibition may therefore be a promising strategy to restore host antitumor immunity and to enhance the antitumor potential of current chemotherapy or immunotherapy for advanced ovarian cancer.