title: Immune checkpoint inhibitors in gynecologic cancers with lessons learned from non-gynecologic cancers.
abstract: The immune system plays a critical role in controlling cancer through a dynamic relationship with cancer cells. Immunotherapy can establish a sustained immune response against recurring cancer cells leading to long-term remissions for cancer patients. The use of immune checkpoint inhibitors, which work by targeting molecules that regulate immune responses, might be a promising avenue of immunotherapeutic research in gynecologic cancers.
  
  
  
  This review focuses on the use of immune checkpoint inhibitors targeting cytotoxic T lymphocyte antigen-4 (CTLA-4) and the programmed death receptors such as PD-1 and PD1-ligand in gynecologic cancers. Combinatorial approaches utilizing immunotherapeutic agents with conventional treatments as well as immune-related response criteria and the adverse effects arising due to checkpoint inhibitor immunotherapy have been also discussed in the review.
  
  
  
  After years of very little success, a better understanding of the pivotal role of the tumor microenvironment in suppressing anticancer immunity and the exploration of treatment regimens using immune checkpoint inhibitors alone or in combination have finally led to the development of effective cancer immunotherapies and to improve survival of patients with certain types of advanced cancers. While the clinical experience with immune checkpoint inhibitors in gynecologic cancer patients remains limited, early signal of clinical activity strongly suggest that immunotherapy will play a significant role in the year to come in at least a subset of gynecologic cancer patients.
authors.affiliation: a Department of Obstetrics, Gynecology & Reproductive Sciences , Yale University School of Medicine , New Haven , CT , USA.
authors.forename: Gulden
authors.initials: G
authors.lastname: Menderes
authors.affiliation: b Department of Obstetrics and Gynecology , Bridgeport Hospital, Yale New Haven Health , Bridgeport , CT , USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Hicks
authors.affiliation: a Department of Obstetrics, Gynecology & Reproductive Sciences , Yale University School of Medicine , New Haven , CT , USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Black
authors.affiliation: a Department of Obstetrics, Gynecology & Reproductive Sciences , Yale University School of Medicine , New Haven , CT , USA.
authors.forename: Carlton L
authors.initials: CL
authors.lastname: Schwab
authors.affiliation: a Department of Obstetrics, Gynecology & Reproductive Sciences , Yale University School of Medicine , New Haven , CT , USA.
authors.forename: Alessandro D
authors.initials: AD
authors.lastname: Santin
mesh_terms: D060908:CTLA-4 Antigen / Q000276:immunology*; D005260:Female; D005833:Genital Neoplasms, Female / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects; D009364:Neoplasm Recurrence, Local; D059016:Tumor Microenvironment
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human
keywords: Immunotherapy; anti-cytotoxic T-lymphocytes; anti-program death ligands; anti-programmed death agents; checkpoint inhibition; gynecologic cancer