Checkpoint Inhibition and Infectious Diseases: A Good Thing?

Trends Mol Med. 2019 Dec;25(12):1080-1093. doi: 10.1016/j.molmed.2019.08.004. Epub 2019 Sep 4.

Abstract

The mammalian immune system has evolved the capacity to detect and destroy tumor cells. Tumors utilize multiple strategies to evade host immune surveillance, including the induction of the checkpoint molecules cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) to suppress antitumor immunity. Pharmacologic blockade of these molecules with checkpoint inhibitors (CPIs) restores T cell function and prolongs survival in patients with various malignancies. Emerging evidence suggests that the same checkpoint pathways may play a crucial role during infections. Indeed, CPIs appear promising as immunotherapeutic agents in infectious diseases, although their efficacy varies depending on pathogen-, cell-, and organ-specific factors. More research will be necessary to clarify the effects and safety of CPIs on clinically relevant outcomes of human infection.

Keywords: checkpoint inhibitors; immune checkpoint; immunotherapy; infection; infectious diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bacterial Infections / immunology
  • Bacterial Infections / therapy*
  • CTLA-4 Antigen / immunology
  • Humans
  • Immunotherapy / methods
  • Mycoses / immunology
  • Mycoses / therapy*
  • Parasitic Diseases / immunology
  • Parasitic Diseases / therapy*
  • Programmed Cell Death 1 Receptor / immunology
  • T-Lymphocytes / immunology
  • Virus Diseases / immunology
  • Virus Diseases / therapy*

Substances

  • CTLA-4 Antigen
  • Programmed Cell Death 1 Receptor