Restoration of HBV-specific CD8+ T cell function by PD-1 blockade in inactive carrier patients is linked to T cell differentiation

Bengsch, Bertram; Martin, Bianca; Thimme, Robert

doi:10.1016/j.jhep.2014.07.005

Cited by 244 publications

(194 citation statements)

References 29 publications

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“…More recently, it has been described that exhaustion of HBV-and HCVspecific CD8+ T-cells is associated with increased expression of inhibitory receptors such as PD-1, 2B4, CTLA-4, Tim-3, the pro-apoptotic molecule Bim and CD39 [47] . Indeed, most exhausted HBV-and HCV-specific CD8+ T-cells express several of these receptors [48,49] . These activate partially redundant pathways and act partially synergistic, explaining that blockade of a single inhibitory receptor type is not sufficient to restore antiviral function.…”

Section: Failure Of Hbv-and Hcv-specific Cd8+ T-cell Response: T-cellmentioning

confidence: 99%

CD8+ T-Cell Responses in Hepatitis B and C: The (HLA-) A, B, and C of Hepatitis B and C

Nitschke

Luxenburger

Kiraithe

et al. 2016

Dig Dis

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Approximately 500 million people are chronically infected with the hepatitis B virus (HBV) or hepatitis C virus (HCV) worldwide and are thus at high risk of progressive liver disease, leading to liver fibrosis, cirrhosis and ultimately hepatocellular cancer. Virus-specific CD8+ T-cells play a major role in viral clearance in >90% of adult patients who clear HBV and in approximately 30% of patients who clear HCV in acute infection. However, several mechanisms contribute to the failure of the adaptive CD8+ T-cell response in those patients who progress to chronic infection. These include viral mutations leading to escape from the CD8+ T-cell response as well as exhaustion and dysfunction of virus-specific CD8+ T-cells. Antiviral efficacy of the virus-specific CD8+ T-cell response also strongly depends on its restriction by specific human leukocyte antigens (HLA) class I alleles. Our review will summarize the role of HLA-A, B and C-restricted CD8+ T-cells in HBV and HCV infection. Due to the current lack of a comprehensive database of HBV- and HCV-specific CD8+ T-cell epitopes, we also provide a summary of the repertoire of currently well-described HBV- and HCV-specific CD8+ T-cell epitopes. A better understanding of the factors that contribute to the success or failure of virus-specific CD8+ T-cells may help to develop new therapeutic options for HBV eradication in patients with chronic HBV infection (therapeutic vaccination and/or immunomodulation) as well as a prophylactic vaccine against HCV infection.

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Section: Failure Of Hbv-and Hcv-specific Cd8+ T-cell Response: T-cellmentioning

confidence: 99%

CD8+ T-Cell Responses in Hepatitis B and C: The (HLA-) A, B, and C of Hepatitis B and C

Nitschke

Luxenburger

Kiraithe

et al. 2016

Dig Dis

Self Cite

View full text Add to dashboard Cite

show abstract

“…In contrast, in patients with chronic HBV infection CD8 + T cell immune responses are weak and oligospecific [6], which is possibly promoted by induction of T cell tolerance by the HBeAg [7]. But also in HBeAg-negative hepatitis B, continuous exposure to viral antigens leads to T cell exhaustion [8,9] and potentially ultimate physical deletion of virus-specific CD8 + T cells by upregulation of pro-apoptotic molecules [10,11]. Accordingly, for successful immunotherapies treatment-induced suppression of viral replication in combination with strategies to rescue antiviral CD8 + T cell function is considered to be essential [9,[12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Decades after recovery from hepatitis B and HBsAg clearance the CD8+ T cell response against HBV core is nearly undetectable

Kefalakes

Jochum

Hilgard

et al. 2015

Journal of Hepatology

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“…Blocking the PD-1/PD-L1 interaction in vitro reversed exhausted cytokine production and proliferation of these HBV specific T cells [53][54][55]. This approach has been generating striking results in immuno-oncology area.…”

Section: Developing New Medicines For Chbmentioning

confidence: 98%

Two Types of Viral Hepatitis, Two Different Treats from Pharma -What’s After the Liver Meeting® 2014?

Yunfen¹

2015

JHVRV

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Restoration of HBV-specific CD8+ T cell function by PD-1 blockade in inactive carrier patients is linked to T cell differentiation

Cited by 244 publications

References 29 publications

CD8+ T-Cell Responses in Hepatitis B and C: The (HLA-) A, B, and C of Hepatitis B and C

CD8+ T-Cell Responses in Hepatitis B and C: The (HLA-) A, B, and C of Hepatitis B and C

Decades after recovery from hepatitis B and HBsAg clearance the CD8+ T cell response against HBV core is nearly undetectable

Two Types of Viral Hepatitis, Two Different Treats from Pharma -What’s After the Liver Meeting® 2014?

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