Related Experiment Video

Updated: Jun 30, 2025

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
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Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

15.1K

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

Daniela Chmiest1, Silvia Podavini1, Kalliopi Ioannidou2

  • 1Department of Immunobiology, University of Lausanne, Epalinges, Switzerland.

Blood Advances
|March 21, 2024
PubMed

Insights

Programmed cell death protein 1 (PD1) inhibition impacts T-cell function by blocking protein kinase Cθ (PKCθ) and vimentin phosphorylation. This suggests vimentin phosphorylation levels could predict response to PD1-based cancer immunotherapies.

Area of Science:

  • Immunology
  • Cell Biology
  • Cancer Research

Background:

  • Programmed cell death protein 1 (PD1) is a key target in cancer immunotherapy, but treatment response varies.
  • Understanding PD1's intracellular mechanisms is crucial for developing better biomarkers.
  • Current knowledge of PD1's downstream signaling pathways requires further elucidation.

Purpose of the Study:

  • To investigate the intracellular pathways affected by PD1 engagement in human T cells.
  • To identify novel biomarkers for predicting response to PD1-based cancer immunotherapies.
  • To elucidate the role of protein kinase Cθ (PKCθ) in PD1-mediated T-cell inhibition.

Main Methods:

  • Unbiased phosphoproteome analysis of primary human T cells.
  • Assessment of PKCθ activation and immune synapse (IS) formation.
  • Analysis of vimentin phosphorylation in T cells and correlation with PD1 ligand (PDL1) levels in lung carcinoma.

Main Results:

  • PD1 triggering inhibited phosphorylation and association of cytoskeleton proteins with PKCθ.
  • PD1 blockade of PKCθ recruitment to the IS was dependent on SHP1/SHP2 phosphatases.
  • PD1 engagement resulted in impaired synaptic phosphorylation and smaller IS formation.
  • T-cell receptor-induced vimentin phosphorylation was inhibited by PD1, and this correlated inversely with PDL1 levels in lung cancer.

Conclusions:

  • PKCθ and its substrate vimentin are critical targets of PD1-mediated T-cell inhibition.
  • PD1 signaling disrupts T-cell immune synapse formation and function.
  • Vimentin phosphorylation levels may serve as a predictive biomarker for PD1 pathway activation in cancer patients.

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