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

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

Author information

1
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA; email: mhashi4@emory.edu , akamphorst@emory.edu , sejin.im@emory.edu , karaki@emory.edu , rahmed@emory.edu.
2
Department of Urology, Emory University School of Medicine, Atlanta, Georgia 30322, USA; email: haydn.kissick@emory.edu.
3
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA; email: rnpilla@emory.edu , ssramal@emory.edu.

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

[Indexed for MEDLINE]

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