Restoring function in exhausted CD8 T cells during chronic viral infection

By Daniel L. Barber, E. Wherry, D. Masopust, Baogong Zhu, James P. Allison, Arlene H. Sharpe, G. Freeman, Rafi Ahmed. Nature, 2006

4,217 citations recorded by the source corpus.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/789f00c08787a3fe37f5a602bd58d05fef3774b1

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. Rafi Ahmed
2. E. Wherry
3. D. Pardoll
4. Lieping Chen
5. Arlene H. Sharpe
6. Shane Crotty
7. G. Freeman
8. A. Schietinger

In Oncology

1. Lieping Chen
2. D. Pardoll
3. E. Wherry
4. W. Zou
5. Arlene H. Sharpe
6. G. Freeman
7. A. Schietinger
8. J. Wolchok

Citations in the corpus

• Redefining chronic viral infection. (2009, positive): “The inhibitory receptor PD-1, a CD28 family costimulatory/coinhibitory molecule, regulates CD8 T cell exhaustion during chronic LCMV infection in mice (Barber et al., 2006; Wherry et al., 2007).”
• MAP Kinase Inhibition Promotes T Cell and Anti-tumor Activity in Combination with PD-L1 Checkpoint Blockade. (2016, background): “Persistent TCR stimulation drives expression of negative regulators such as PD-1 and leads to exhaustive T cell differentiation during chronic virus infection (Barber et al., 2006) and possibly in cancer (Terheyden et al., 2003).”
• PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy (2015, background): “Upregulated PD-L1 on these cells binds PD-1 on T cells, contributing to the development of T-cell exhaustion (15).”
• PD-L1 expression in human cancers and its association with clinical outcomes (2016, positive): “In chronically infected mice model, high expression of PD-1 on T cells leads to T cell exhaustion and makes the exhausted CD8+ T cells lose effector function of secreting cytokines such as IL-2, IFN-γ, and TNF-α.(18) Binding of PD-L1 to PD-1 leads to the formation of PD-1/TCR inhibitory microcluster”
• Bioenergetic insufficiencies due to metabolic alterations regulated by PD-1 are an early driver of CD8+ T cell exhaustion (2016, result): “PD-L1 blockade resulted in an expansion of virusspecific T cells associated with lower viral load (data not shown), as previously described (Barber et al., 2006).”
• Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. (2014, positive): “In contrast, some viruses can induce PD-L1/PD-1 signaling to escape the host immune response by inducing T cell exhaustion, which results in chronic infection (18–20).”