CD8 T Cell Exhaustion in Chronic Infection and Cancer: Opportunities for Interventions

Annu Rev Med. 2018 Jan 29:69:301-318. doi: 10.1146/annurev-med-012017-043208.

Abstract

Antigen-specific CD8 T cells are central to the control of chronic infections and cancer, but persistent antigen stimulation results in T cell exhaustion. Exhausted CD8 T cells have decreased effector function and proliferative capacity, partly caused by overexpression of inhibitory receptors such as programmed cell death (PD)-1. Blockade of the PD-1 pathway has opened a new therapeutic avenue for reinvigorating T cell responses, with positive outcomes especially for patients with cancer. Other strategies to restore function in exhausted CD8 T cells are currently under evaluation-many in combination with PD-1-targeted therapy. Exhausted CD8 T cells comprise heterogeneous cell populations with unique differentiation and functional states. A subset of stem cell-like PD-1+ CD8 T cells responsible for the proliferative burst after PD-1 therapy has been recently described. A greater understanding of T cell exhaustion is imperative to establish rational immunotherapeutic interventions.

Keywords: PD-1; T cell exhaustion; cancer; checkpoint inhibitors; chronic infection; immunotherapy.

Publication types

  • Review

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Chronic Disease
  • Humans
  • Immunotherapy / methods
  • Infections / drug therapy
  • Infections / immunology*
  • Lymphocytic Choriomeningitis / drug therapy
  • Lymphocytic Choriomeningitis / immunology
  • Neoplasms / drug therapy
  • Neoplasms / immunology*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • T-Lymphocyte Subsets / immunology*
  • Virus Diseases / drug therapy
  • Virus Diseases / immunology

Substances

  • Programmed Cell Death 1 Receptor