Determinants of Resistance to Checkpoint Inhibitors

Int J Mol Sci. 2020 Feb 26;21(5):1594. doi: 10.3390/ijms21051594.

Abstract

The development of immune checkpoint inhibitors (ICIs) has drastically altered the landscape of cancer treatment. Since approval of the first ICI for the treatment of advanced melanoma in 2011, several therapeutic agents have been Food and Drug Administration (FDA)-approved for multiple cancers, and hundreds of clinical trials are currently ongoing. These antibodies disrupt T-cell inhibitory pathways established by tumor cells and thus re-activate the host's antitumor immune response. While successful in many cancers, several types remain relatively refractory to treatment or patients develop early recurrence. Hence, there is a great need to further elucidate mechanisms of resistant disease and determine novel, effective, and tolerable combination therapies to enhance efficacy of ICIs.

Keywords: cancer; combination therapy; functional genomics; immune checkpoint inhibitors; immune checkpoints; immunotherapy; next generation sequencing; predictive markers; prognostic markers.

Publication types

  • Review

MeSH terms

  • Combined Modality Therapy / methods
  • Drug Resistance, Neoplasm / genetics
  • Drug Resistance, Neoplasm / physiology
  • Genomics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immune Checkpoint Inhibitors / immunology
  • Immune Checkpoint Inhibitors / pharmacology*
  • Immunotherapy / methods
  • Melanoma / drug therapy*
  • Melanoma / genetics
  • Melanoma / immunology
  • T-Lymphocytes
  • Tumor Microenvironment

Substances

  • Immune Checkpoint Inhibitors