Immunotherapy: New Strategies for the Treatment of Gynecologic Malignancies

Abstract

Over the past decade, the ability of cancer cells to evade immune destruction has become recognized as one of the hallmarks of cancer. This understanding has paved the way for the development of novel therapeutic agents that can enhance activation of antitumor immune responses or reverse immunosuppressive mechanisms through which tumors escape immune-mediated rejection. The treatment of gynecologic cancers remains a therapeutic challenge, as these malignancies are often diagnosed in advanced stages, and many patients relapse despite appropriate management. Clinical trials have shown efficacy for various immunotherapeutic strategies, especially the use of tumor-targeting antibodies; enhancement of tumor antigen presentation, such as with vaccines and toll-like receptor agonists; and the targeting of immunosuppressive mechanisms, such as via checkpoint blockade. Emerging data on new and combination approaches currently under investigation provide a strong rationale for these approaches.

Figure. Opportunities for Immunotherapy in Gynecologic Malignancies

Successful immunotherapy for gynecologic cancers will require multimodal approaches that target different aspects of the antitumor immune response, including tumor antigen recognition, T-cell activation, and blockade of immune inhibitory mechanisms. Strategies currently in development are presented in boxes. APC = antigen-presenting cell; CTLA-4 = cytotoxic T-lymphocyte–associated antigen 4; GITR = glucocorticoid-induced tumor necrosis factor receptor–related protein; IDO = indoleamine 2,3-dioxygenase; MDSC = myeloid-derived suppressor cell; MHC = major histocompatibility complex; TAAs = tumor-associated antigens; TCR = T-cell receptor; TLR = toll-like receptor; Treg = regulatory T cell.