Immunotherapy in Gynecologic Cancers: Are We There Yet?

Abstract

Opinion statement Immune-targeted therapies have demonstrated durable responses in many tumor types with limited treatment options and poor overall prognosis. This has led to enthusiasm for expanding such therapies to other tumor types including gynecologic malignancies. The use of immunotherapy in gynecologic malignancies is in the early stages and is an active area of ongoing clinical research. Both cancer vaccines and immune checkpoint inhibitor therapy continue to be extensively studied in gynecologic malignancies. Immune checkpoint inhibitors, in particular, hold promising potential in specific subsets of endometrial cancer that express microsatellite instability. The key to successful treatment with immunotherapy involves identification of the subgroup of patients that will derive benefit. The number of ongoing trials in cervical, ovarian, and endometrial cancer will help to recognize these patients and make treatment more directed. Additionally, a number of studies are combining immunotherapy with standard treatment options and will help to determine combinations that will enhance responses to standard therapy. Overall, there is much enthusiasm for immunotherapy approaches in gynecologic malignancies. However, the emerging data shows that with the exception of microsatellite unstable tumors, the use of single-agent immune checkpoint inhibitors is associated with response rates of 10– 15%. More effective and likely combinatorial approaches are needed and will be informed by the findings of ongoing trials.

The immune microenvironment of uterine adenosarcomas

“…Several reported and ongoing trials have looked into the role of checkpoint inhibitors in ovarian, cervical and endometrial cancers. In a trial of 20 patients involving the use of nivolumab [26], an anti-PD-1 antibody in ovarian cancer has shown a response rate of 15% and disease control rate of 45%. However, results in soft tissue sarcoma trials have been less promising.…”

Ovarian cancer: Current status and strategies for improving therapeutic outcomes

“…Cancer Vaccine therapeutic investigation is an actively growing area in OC research. Currently, there are mainly pilot and phase I or II trials on the use of therapeutic vaccines in OC . A list of ongoing vaccine studies in OC (Source: http://www.ClinicalTrial.gov) is given in Table .…”

“…Activated T lymphocyte functions as an inhibitor via "negative feedback loop" mechanism and protect normal tissues from tumor-derived immune response. 85 These proteins are over expressed in OC patients and their natural anti-cancer immunity is at disadvantage. Currently, several monoclonal antibodies (mAb) against CTLA-4 and other proteins and its ligand are used in clinics.…”

“…Currently, there are mainly pilot and phase I or II trials on the use of therapeutic vaccines in OC. 85,96 A list of ongoing vaccine studies in OC (Source: www.Clini calTr ial.gov) is given in Table S4. NY-ESO-1, a potential molecule for targeted vaccine due to its over expression in OC exhibited stimulated immune response specific to T cells. 97 Combination therapy of NY-ESO-1 with DNA methylation inhibitors and chemotherapy was administered in patients with recurrent disease for therapeutic efficacy enhancement.…”

Tanshinone IIA effects on ovarian cancer cell line

“…The targeted therapies such as bevacizumab (Avastin) and olaparib (Lynparza) are the emerging treatments with great promise, while the clinical outcomes are still to be proofed . In addition, monoclonal antibodies, immune checkpoint inhibitors and modulators, therapeutic vaccines, adoptive T‐cell transfer, oncolytic viruses and adjuvant immunotherapies are in early‐phase testing for deadly ovarian cancer . Therefore, the revolutionary therapeutics remain in urgent need and request further understanding into the biology of ovarian cancer at molecular level.…”