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- W2043579427 abstract "The inhibitory receptor programmed cell death 1 (PD-1) plays a major role in functional exhaustion of T cells during chronic infections and cancer, and recent clinical data suggest that blockade of the PD-1 pathway is an effective immunotherapy in treating certain cancers. Thus, it is important to define combinatorial approaches that increase the efficacy of PD-1 blockade. To address this issue, we examined the effect of IL-2 and PD-1 ligand 1 (PD-L1) blockade in the mouse model of chronic lymphocytic choriomeningitis virus (LCMV) infection. We found that low-dose IL-2 administration alone enhanced CD8+ T cell responses in chronically infected mice. IL-2 treatment also decreased inhibitory receptor levels on virus-specific CD8+ T cells and increased expression of CD127 and CD44, resulting in a phenotype resembling that of memory T cells. Surprisingly, IL-2 therapy had only a minimal effect on reducing viral load. However, combining IL-2 treatment with blockade of the PD-1 inhibitory pathway had striking synergistic effects in enhancing virus-specific CD8+ T cell responses and decreasing viral load. Interestingly, this reduction in viral load occurred despite increased numbers of Tregs. These results suggest that combined IL-2 therapy and PD-L1 blockade merits consideration as a regimen for treating human chronic infections and cancer." @default.
- W2043579427 created "2016-06-24" @default.
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- W2043579427 date "2013-05-15" @default.
- W2043579427 modified "2023-10-16" @default.
- W2043579427 title "PD-L1 blockade synergizes with IL-2 therapy in reinvigorating exhausted T cells" @default.
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- W2043579427 doi "https://doi.org/10.1172/jci67008" @default.
- W2043579427 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3668811" @default.
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- W2043579427 hasPublicationYear "2013" @default.
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