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Burke K, Grebinoski S, Sharpe A, Vignali D.
Understanding adverse events of immunotherapy: A mechanistic perspective. Journal of Experimental Medicine. 2020;218.
Sage P, Sharpe A.
The multifaceted functions of follicular regulatory T cells. Current Opinion in Immunology. 2020;67 :68-74.
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Abstract
The PD-1 pathway regulates dysfunctional T cells in chronic infection and cancer, but the role of this pathway during acute infection remains less clear. Here, we demonstrate that PD-1 signals are needed for optimal memory. Mice deficient in the PD-1 pathway exhibit impaired CD8+ T cell memory following acute influenza infection, including reduced virus-specific CD8+ T cell numbers and compromised recall responses. PD-1 blockade during priming leads to similar differences early post-infection but without the defect in memory formation, suggesting that timing and/or duration of PD-1 blockade could be tailored to modulate host responses. Our studies reveal a role for PD-1 as an integrator of CD8+ T cell signals that promotes CD8+ T cell memory formation and suggest PD-1 continues to fine-tune CD8+ T cells after they migrate into nonlymphoid tissues. These findings have important implications for PD-1-based immunotherapy, in which PD-1 inhibition may influence memory responses in patients.
PubMed DOI
LaFleur MW, Miller BC, Sharpe AH.
Prevention of CAR-T-cell dysfunction. Nat Biomed Eng. 2020;4 (1) :16-17.
Abstract
The overexpression of the transcription factor c-Jun improves chimeric-antigen-receptor T-cell functionality and enhances the killing of low-antigen-expressing liquid and solid cancers in mice.
PubMed DOI
