Immune Checkpoint Blockade for Breast Cancer

Cancer Treat Res. 2018:173:155-165. doi: 10.1007/978-3-319-70197-4_10.

Abstract

An effective antitumor immune response requires interaction between cells of the adaptive and innate immune system. Three key elements are required: generation of activated tumor-directed T cells, infiltration of activated T cells into the tumor microenvironment, and killing of tumor cells by activated T cells. Tumor immune evasion can occur as a result of the disruption of each of these three key T cell activities, resulting in three distinct cancer-immune phenotypes. The immune inflamed phenotype, characterized by the presence of a robust tumor immune infiltrate, suggests impaired activated T cell killing of tumor cells related to the presence of inhibitory factors. Programmed death receptor-1 (PD-1) is an inhibitory transmembrane protein expressed on T cells, B cells, and NK cells. The interaction between PD-1 and its ligands (PD-L1/L2) functions as an immune checkpoint against unrestrained cytotoxic T effector cell activity-it promotes peripheral T effector cell exhaustion and conversion of T effector cells to immunosuppressive T regulatory (Treg) cells. Immune checkpoint inhibitors, which block the PD-1/PD-L1 axis and reactivate cytotoxic T effector cell function, are actively being investigated for the treatment of breast cancer.

Keywords: Breast cancer; Immune checkpoint inhibitors; Immunotherapy.

Publication types

  • Review

MeSH terms

  • B7-H1 Antigen / analysis*
  • B7-H1 Antigen / antagonists & inhibitors
  • Breast Neoplasms / drug therapy*
  • Female
  • Humans
  • Immunotherapy
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*

Substances

  • B7-H1 Antigen
  • Programmed Cell Death 1 Receptor