Evidence map›Paper›PMID 38513140›Full record

ArticleBlood advances2024

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

Daniela Chmiest, Silvia Podavini, Kalliopi Ioannidou, David Vallois, Chantal Décaillet, Montserrat Gonzalez, Manfredo Quadroni, Kevin Blackney, Rebekka Schairer, Laurence de Leval and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Blood advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 31% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Review
  3. Regulatory T cells attenuate astrogliosis via IL-10/STAT3/PKC/vimentin signaling and promote neurological recovery after spinal cord injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

Daniela ChmiestDepartment of Immunobiology, University of Lausanne, Epalinges, Switzerland.
Silvia PodaviniDepartment of Immunobiology, University of Lausanne, Epalinges, Switzerland.ORCID 0009-0001-0704-5506
Kalliopi IoannidouDepartment of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
David ValloisDepartment of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Chantal DécailletDepartment of Immunobiology, University of Lausanne, Epalinges, Switzerland.
Montserrat GonzalezDepartment of Immunobiology, University of Lausanne, Epalinges, Switzerland.
Manfredo QuadroniProtein Analysis Facility, University of Lausanne, Lausanne, Switzerland.ORCID 0000-0002-2720-4084
Kevin BlackneyFlow Cytometry Facility, Department of Formation and Research, University of Lausanne, Epalinges, Switzerland.
Rebekka SchairerDepartment of Internal Medicine II, Hematology, Oncology, Clinical Immunology, and Rheumatology, University Hospital Tübingen, Tübingen, Germany.
Laurence de LevalDepartment of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Margot ThomeDepartment of Immunobiology, University of Lausanne, Epalinges, Switzerland.ORCID 0000-0002-5656-2139
University of Lausanne · CHHôpital Orthopédique de la Suisse Romande · CHUniversity Children's Hospital Tübingen · DEUniversity Hospital of Lausanne · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

abstractThe inhibitory surface receptor programmed cell death protein 1 (PD1) is a major target for antibody-based cancer immunotherapies. Nevertheless, a substantial number of patients fail to respond to the treatment or experience adverse effects. An improved understanding of intracellular pathways targeted by PD1 is thus needed to develop better predictive and prognostic biomarkers. Here, via unbiased phosphoproteome analysis of primary human T cells, we demonstrate that PD1 triggering inhibited the phosphorylation and physical association with protein kinase Cθ (PKCθ) of a variety of cytoskeleton-related proteins. PD1 blocked activation and recruitment of PKCθ to the forming immune synapse (IS) in a Src homology-2 domain-containing phosphatase-1/2 (SHP1/SHP2)-dependent manner. Consequently, PD1 engagement led to impaired synaptic phosphorylation of cytoskeleton-related proteins and formation of smaller IS. T-cell receptor induced phosphorylation of the PKCθ substrate and binding partner vimentin was long-lasting and it could be durably inhibited by PD1 triggering. Vimentin phosphorylation in intratumoral T cells also inversely correlated with the levels of the PD1 ligand, PDL1, 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 may serve as a biomarker for the activation of the PD1 pathway.

Indexed as

Immunological SynapsesProgrammed Cell Death 1 ReceptorProtein Kinase C-thetaB7-H1 AntigenCytoskeletal ProteinsHumansPhosphorylationProtein Kinase CT-LymphocytesVimentinB7-H1 AntigenCD274 protein, humanCytoskeletal ProteinsPDCD1 protein, humanPRKCQ protein, humanProgrammed Cell Death 1 ReceptorProtein Kinase CProtein Kinase C-thetaVimentin

Identifiers

PMID38513140
PMCPMC11176957
OpenAlexW4393057489

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.