PD-L1/PD-1 axis as a potent therapeutic target in breast cancer

Life Sci. 2020 Apr 15:247:117437. doi: 10.1016/j.lfs.2020.117437. Epub 2020 Feb 16.

Abstract

Although both the incidence and the mortality rate of breast cancer is rising, there is no potent and practical option for the treatment of these patients, particularly in advanced stages. One of the most critical challenges for treatment is the presence of complicated and extensive tumor escape mechanisms in the tumor microenvironment. Immune checkpoint molecules are of the main immunosuppressive mechanisms used by cancerous cells to block anti-cancer immune responses. Among these molecules, PD-1 (Programmed cell death) and PD-L1 (programmed cell death-ligand 1) have been considered as worthy therapeutic targets for breast cancer therapy. In this review, we intend to discuss the immunobiology and signaling of the PD-1/PD-L1 axis and highlight its importance as a worthy therapeutic target in breast cancer. We believe that the prognostic value of PD-L1 depends on the breast cancer subtype. Moreover, the combination of PD-1/PD-L1 targeting with immune-stimulating vaccines can be considered as an effective therapeutic strategy in breast cancer.

Keywords: Breast cancer; Immune checkpoint; Immunotherapy; PD-1; PD-L1.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / therapeutic use
  • B7-H1 Antigen / chemistry
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism*
  • Breast Neoplasms / drug therapy*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Immunotherapy
  • Molecular Targeted Therapy / methods*
  • Programmed Cell Death 1 Receptor / chemistry
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism*
  • Protein Binding / drug effects
  • Protein Conformation
  • Signal Transduction
  • T-Lymphocytes / drug effects
  • Tumor Escape / drug effects
  • Tumor Microenvironment / drug effects

Substances

  • Antineoplastic Agents
  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor