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

2018/01/29 by Masao Hashimoto, Alice O. Kamphorst, Se Jin Im +6 · 11 citations
Immunology and Microbiology · Medicine · #Immune Cell Function and Interaction #Cancer Immunotherapy and Biomarkers #CAR-T cell therapy research

paper · pdf · 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.

Citations

• Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma

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