%0 Journal Article 
%A Peña Asensio, Julia
%A Calvo Sánchez, Henar
%A Torralba González de Suso, Miguel
%A Miquel Plaza, Joaquín
%A Sanz de Villalobos, Eduardo
%A Larrubia Marfil, Juan Ramón
%T Gamma-Chain Receptor Cytokines & PD-1 Manipulation to Restore HCV-Specific CD8 + T Cell Response during Chronic Hepatitis C
%D 2021
%@ 2073-4409
%U http://hdl.handle.net/10017/50987
%X Hepatitis C virus (HCV)-specific CD8+ T cell response is essential in natural HCV infection control, but it becomes exhausted during persistent infection. Nowadays, chronic HCV infection can be resolved by direct acting anti-viral treatment, but there are still some non-responders that could benefit from CD8+ T cell response restoration. To become fully reactive, T cell needs the complete release of T cell receptor (TCR) signalling but, during exhaustion this is blocked by the PD-1 effect on CD28 triggering. The T cell pool sensitive to PD-1 modulation is the progenitor subset but not the terminally differentiated effector population. Nevertheless, the blockade of PD-1/PD-L1 checkpoint cannot be always enough to restore this pool. This is due to the HCV ability to impair other co-stimulatory mechanisms and metabolic pathways and to induce a pro-apoptotic state besides the TCR signalling impairment. In this sense, gamma-chain receptor cytokines involved in memory generation and maintenance, such as low-level IL-2, IL-7, IL-15, and IL-21, might carry out a positive effect on metabolic reprogramming, apoptosis blockade and restoration of co-stimulatory signalling. This review sheds light on the role of combinatory immunotherapeutic strategies to restore a reactive anti-HCV T cell response based on the mixture of PD-1 blocking plus IL-2/IL-7/IL-15/IL-21 treatment.
%K CD8+ T cell response
%K Hepatitis C virus
%K IL-15
%K IL-2
%K IL-21
%K IL-7
%K PD-1
%K PD-L1
%K Exhaustion
%K Immune checkpoints
%K Gamma-chain cytokines
%K Medicina
%K Medicine
%~ Biblioteca Universidad de Alcala