ArticlePloS one2018
Mathematical modeling identifies Lck as a potential mediator for PD-1 induced inhibition of early TCR signaling.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Cancer cell immunity-related protein co-expression networks are associated with early-stage solid-predominant lung adenocarcinoma.Frontiers in oncology · 2024Article
- Disulfiram's journey from rubber vulcanization to T-cell activation.The EMBO journal · 2022Article
- MECHANISTIC AND DATA-DRIVEN MODELS OF CELL SIGNALING: TOOLS FOR FUNDAMENTAL DISCOVERY AND RATIONAL DESIGN OF THERAPY.Current opinion in systems biology · 2021Article
- Systematic identification of the cancer pathways and molecules related with breast cancer immunogenicity.Medical oncology (Northwood, London, England) · 2021Article
- Autophosphorylation and the Dynamics of the Activation of Lck.Bulletin of mathematical biology · 2021Article
- Identification of a Sensitive Human Immunological Target of Aryl Hydrocarbon Receptor Activation: CD5Frontiers in immunology · 2021Article
- Naturally Occurring Genetic Alterations in Proximal TCR Signaling and Implications for Cancer Immunotherapy.Frontiers in immunology · 2021Review
- Multi-Level Computational Modeling of Anti-Cancer Dendritic Cell Vaccination Utilized to Select Molecular Targets for Therapy Optimization.Frontiers in cell and developmental biology · 2021Article
- A compiler for biological networks on silicon chips.PLoS computational biology · 2020Article
- Modeling immune cell behavior across scales in cancer.Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- Toward Systems Biomarkers of Response to Immune Checkpoint Blockers.Frontiers in oncology · 2020Review
- Integrative Approaches to Cancer Immunotherapy.Trends in cancer · 2019Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Programmed cell death-1 (PD-1) is an inhibitory immune checkpoint receptor that negatively regulates the functioning of T cell. Although the direct targets of PD-1 were not identified, its inhibitory action on the TCR signaling pathway was known much earlier. Recent experiments suggest that the PD-1 inhibits the TCR and CD28 signaling pathways at a very early stage ─ at the level of phosphorylation of the cytoplasmic domain of TCR and CD28 receptors. Here, we develop a mathematical model to investigate the influence of inhibitory effect of PD-1 on the activation of early TCR and CD28 signaling molecules. Proposed model recaptures several quantitative experimental observations of PD-1 mediated inhibition. Model simulations show that PD-1 imposes a net inhibitory effect on the Lck kinase. Further, the inhibitory effect of PD-1 on the activation of TCR signaling molecules such as Zap70 and SLP76 is significantly enhanced by the PD-1 mediated inhibition of Lck. These results suggest a critical role for Lck as a mediator for PD-1 induced inhibition of TCR signaling network. Multi parametric sensitivity analysis explores the effect of parameter uncertainty on model simulations.
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