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

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

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.

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

Publication types

  • Review

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
  • Combined Modality Therapy* / methods
  • Female
  • Humans
  • Mice, Inbred C57BL
  • Neoplasm Staging
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / therapy*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / physiology
  • Radiotherapy
  • Signal Transduction
  • Tumor Microenvironment

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor