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ID persistente
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doi:10.21950/P2RKZB |
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Fecha de publicación
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2017-05-03 |
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Título
| Signalling adaptor TRAF1 modulation, as a therapeutic target, to restore HCV-specific cytotoxic T cell response reactivity during chronic infection |
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Autor
| Larrubia, Juan-RamónDepartment of Medicine and Medical Specialties. University of Alcalá (UAH); Translational Hepatology Unit. Section of Digestive Diseases. Hospital Universitario de Guadalajara. SpainORCIDhttp://orcid.org/0000-0002-6383-848X
Moreno-Cubero, EliaDepartment of Biology of Systems. University of Alcalá (UAH); Translational Hepatology Unit. Section of Digestive Diseases. Hospital Universitario de Guadalajara. Spain |
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Contacto
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Utilice el botón de e-mail de arriba para contactar.
Larrubia, Juan-Ramón (Department of Medicine and Medical Specialties. University of Alcalá (UAH)) |
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Descripción
| Hepatitis C virus (HCV) worldwide infects around 170 million people. Two thirds of primo-infections develop a chronic disease that could lead to cirrhosis and hepatocellular carcinoma. This infection can be cured with direct acting anti-virals (DAA) but there are still difficult to treat cases relapsing after treatment, in which immunotherapy could play a role in curation. A successful immune response against HCV depends on virus-specific CD8+ T cells. During chronic infection, these cells are functionally impaired. The degree of this immune impairment could rely on the grade of co-stimulation failure over time of infection. The analysis of this dataset shows that: (1) Patients with short-mid lasting HCV infection had mild exhausted T cells, featured by loss of the key signal transducer (TRAF1) of the positive checkpoint 4-1BB/4-1BBL. (2) The functionality of these cells can be restored by IL-7-induced TRAF1 up-regulation, while in long-lasting infection to block the negative-costimulatory pathway PD-1/PD-L1 was also necessary. (3) Nevertheless, this last strategy was only useful in slow-fibrosers, suggesting an extreme T cell exhaustion or deletion in rapid fibrosers. In sum, our work supports novel ways of restoring specific CD8+ T cell response during chronic HCV infection, shedding light on the importance of TRAF1 signalling, which could be a promising target for immunotherapy in non-responders to DAA. (2017-05-03) |
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Materia
| Ciencias médicas, de la salud y de la vida |
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Palabra clave
| Infectious Diseases
Hepatology
Viral Hepatitis
CD8 T cell response
Exhaustion
Co-stimulation
Immunotherapy
Hepatitis C
4-1BB
TRAF1
CD127
PD-1
Mcl-1 |
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Publicación relacionada
| Moreno, E., Subirá, D., Sanz de Villalobos, E., Parra, T., Madejón, A., Miquel, J., … Larrubia, J. (2018). According to Hepatitis C Virus (HCV) Infection Stage, Interleukin-7 Plus 4-1BB Triggering Alone or Combined with PD-1 Blockade Increases TRAF1lowHCV-Specific CD8+Cell Reactivity. Journal of virology, 2018, v. 92, n. 2, p. 1-23 handle http://hdl.handle.net/10017/32839 http://hdl.handle.net/10017/32839 |
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Notas
| Research Institution: Guadalajara University Hospital. Health Service of Castilla-La Mancha. University of Alcalá, Spain.
VER MAPA |
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Idioma
| Inglés |
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Información de la subvención
| Spanish Ministry of Economy and Competitiveness: PI12/00130
Carlos III Health Institute: PI15/00074 |
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Depositante
| Larrubia, Juan-Ramón |
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Fecha de depósito
| 2017-05-03 |
