Proteomics

Dataset Information

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PD1 inhibits PKCθ-dependent phosphorylation of cytoskeleton-related proteins and immune synapse formation


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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