Immune Checkpoint Blockade in Cancer Immunotherapy: Mechanisms, Clinical Outcomes, and Safety Profiles of PD-1/PD-L1 Inhibitors

Arch Immunol Ther Exp (Warsz). 2020 Nov 13;68(6):36. doi: 10.1007/s00005-020-00601-6.

Abstract

Programmed cell death protein 1 (PD-1) and its ligand PD-L1 are critical for the regulation of T cell exhaustion and activity suppression. Tumor cells expressing immune checkpoints including PD-L1 escape monitoring of T cells from the host immune system. Checkpoint inhibitors are highly promising therapies that function as tumor-suppressing factors via modulation of tumor cell-immune cell interactions as well as boosting T cell-mediated anti-tumor immunity. Notably, PD-1 or PD-L1 monoclonal antibody (mAb) has demonstrated promising therapeutic effects in clinical studies of many types of cancer. These mAbs have caused significant tumor regression with impressive anti-tumor response rates as well as a favorable safety profile in cancer patients. Furthermore, the combination of PD-1/PD-L1 mAbs with other types of anti-tumor agents has also developed to boost the anti-tumor responses and enhance therapeutic effects in cancer patients. This review clarifies the mechanisms of PD-1/PD-L1-mediated anti-cancer immune responses and some clinical studies of mAbs targeting PD-1/PD-L1. The challenges and future of PD-1/PD-L1 blockade therapy are also discussed.

Keywords: Immune checkpoints; Immunotherapy; Monoclonal antibody; PD-1; PD-L1.

Publication types

  • Review

MeSH terms

  • Animals
  • B7-H1 Antigen / antagonists & inhibitors*
  • Drug-Related Side Effects and Adverse Reactions
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Treatment Outcome
  • Tumor Escape
  • Tumor Microenvironment

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Immune Checkpoint Inhibitors
  • Programmed Cell Death 1 Receptor