J Gynecol Oncol.  2017 Sep;28(5):e64. 10.3802/jgo.2017.28.e64.

Programmed death-1 pathway blockade produces a synergistic antitumor effect: combined application in ovarian cancer

Affiliations
  • 1Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. langjh@hotmail.com

Abstract

Programmed death-1 (PD-1) and its ligand are part of the immune checkpoint pathway that down-regulates effector T cells in immune response, thereby causing immune suppression. The PD-1/programmed death-ligand 1 (PD-L1) pathway can be blocked by antibodies to reverse tumor-mediated immunosuppression. However, advanced cancers such as stage III-IV ovarian cancer (OC) and certain types such as ID8 OC (a clone of C57BL/6 mouse OC) may hijack the PD-1/PD-L1 pathway to escape immune attack. When combined with chemotherapy, radiotherapy, targeted therapy, immunotherapy, or other agents, these PD-1/PD-L1 pathway blockages can produce a synergistic antitumor response in OC. Combined immunotherapy significantly prolongs overall survival by changing the tumor microenvironment through processes such as increasing the number of CD4⁺ or CD8⁺ T cells or cytokines in mice with OC and decreasing the number of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). OC patients treated with combined immunotherapy received better prognoses than those treated with monotherapy. This review reflects the move toward novel therapy combinations for OC and discusses these promising immunotherapeutic approaches, which are more cost-effective and effective than other approaches.

Keyword

Immunotherapy; Combined Modality Therapy; Therapeutic Use; Ovarian Neoplasms; Programmed Cell Death 1 Receptor; PD-L1 Protein, Human; Toxicity

MeSH Terms

Animals
Antibodies, Monoclonal/therapeutic use
Antineoplastic Agents/therapeutic use
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
CD4-Positive T-Lymphocytes/immunology
CD8-Positive T-Lymphocytes/immunology
Cell Line, Tumor
*Combined Modality Therapy/adverse effects/methods
Female
Humans
Mice, Inbred C57BL
Neoplasm Staging
Ovarian Neoplasms/drug therapy/immunology/pathology/*therapy
Programmed Cell Death 1 Receptor/*antagonists & inhibitors/physiology
Radiotherapy
Signal Transduction
Tumor Microenvironment
Antibodies, Monoclonal
Antineoplastic Agents
Programmed Cell Death 1 Receptor
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