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- W4366333095 abstract "Abstract Increased understanding of the modulatory pathways controlling CD8 T cell responses has led to the formulation of successful checkpoint inhibitor-based immunotherapies against cancer. However, their effectiveness covers only a few tumor types, motivating the search for novel targets. PTPN1 and PTPN2 are two protein tyrosine phosphatases known to regulate pathways involved in CD8 T cell activation. Herein we investigated the potential effects of conditionally targeted genetic deletion of either or both phosphatases in mouse CD8 T cells and the exploitation of their homology in the catalytic domain as a single pharmacological target. Our results demonstrated that hemizygous deletion of PTPN1 in a PTPN2 deficient background heightens the enhanced effector phenotype already observed in PTPN2 defective CD8 T cells. This effect was reproducible with small-molecule inhibitors simultaneously hindering both phosphatases. Hence, simultaneously downregulating both PTPN1 and PTPN2 acts as a powerful tool for potentiating CD8 cytotoxic responses." @default.
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- W4366333095 date "2023-04-18" @default.
- W4366333095 modified "2023-10-18" @default.
- W4366333095 title "Combined inhibition of homologous PTPN1 and PTPN2 is synergistic in enhancing CD8 T cell effector functions" @default.
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- W4366333095 doi "https://doi.org/10.1101/2023.04.17.537264" @default.
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