PD1 inhibits PKCθ-dependent phosphorylation of cytoskeleton-related proteins and immune synapse formation
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ABSTRACT: The cell surface receptor programmed death 1 (PD1) is a major target for antibody-based cancer immunotherapies. An improved understanding of intracellular pathways targeted by PD1 is needed to develop better predictive and prognostic biomarkers. Here, via unbiased phosphoproteome analysis of primary human T cells, we demonstrate that PD1 triggering reduces the phosphorylation and physical association with PKC theta of a variety of cytoskeletal proteins. TCR-induced phosphorylation of Vimentin, a cytoskeleton protein identified as a PKC theta target and binding partner in our study, was found to be long-lasting and durably inhibited by PD1 triggering, and Vimentin phosphorylation inversely correlated with PDL1 levels in intratumoral T cells in human lung carcinoma. Thus, PKCθ and its substrate Vimentin represent important targets of PD1-mediated T cell inhibition and low levels of Vimentin phosphorylation could be considered as a biomarker indicating PD1 pathway engagement.
INSTRUMENT(S): Orbitrap Fusion, Q Exactive Plus
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Blood Cell, Blood
SUBMITTER: Manfredo Quadroni
LAB HEAD: Margot Thome
PROVIDER: PXD044028 | Pride | 2024-04-19
REPOSITORIES: Pride
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