ArticleThe Journal of clinical investigation2021
CD146 bound to LCK promotes T cell receptor signaling and antitumor immune responses in mice.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Endogenous glucocorticoids and glucocorticoid receptor signaling: Dual regulators of PD-1/PD-L1 immunotherapy efficacy in the tumor microenvironment.Chinese medical journal · 2026Review
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- Iridium complex-loaded biomimetic vesicles enable enhanced photodynamic therapy and immune modulation.Microsystems & nanoengineering · 2026Article
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- Immune genes CD247 STAT1 and LCK mediate host-pathogen interactions in sporotrichosis.Scientific reports · 2025Article
- IFITM1 as a modulator of surfaceome dynamics and aggressive phenotype in cervical cancer cells.Oncology reports · 2025Article
- Melanoma Cell Adhesion Molecule Plays a Pivotal Role in Proliferation, Migration, Tumor Immune Microenvironment, and Immunotherapy in Colorectal Cancer.Cancer medicine · 2025Article
- The TCR and LCK: foundations for T-cell activation and therapeutic innovation.Frontiers in immunology · 2025Review
- Epigenetics behind CD8Genes and immunity · 2024Review
- Focusing on CD8Journal of experimental & clinical cancer research : CR · 2024Review
- CD146, a therapeutic target involved in cell plasticity.Science China. Life sciences · 2024Review
- Lck Function and Modulation: Immune Cytotoxic Response and Tumor Treatment More Than a Simple Event.Cancers · 2024Review
- CD146 promotes resistance of NSCLC brain metastases to pemetrexed via the NF-κB signaling pathway.Frontiers in pharmacology · 2024Article
- Identification of a novel circRNA-miRNA-mRNA regulatory axis in hepatocellular carcinoma based on bioinformatics analysis.Scientific reports · 2023Article
- Small-Molecule Compounds Boost CAR-T Cell Therapy in Hematological Malignancies.Current treatment options in oncology · 2023Review
- Integrative and Comprehensive Pan-Cancer Analysis of Lymphocyte-Specific Protein Tyrosine Kinase in Human Tumors.International journal of molecular sciences · 2022Article
- A novel lipidic peptide with potential to promote balanced effector-regulatory T cell responses.Scientific reports · 2022Article
- Comprehensive analysis of a glycolysis and cholesterol synthesis-related genes signature for predicting prognosis and immune landscape in osteosarcoma.Frontiers in immunology · 2022Article
- Identifying tumor immunity-associated molecular features in liver hepatocellular carcinoma by multi-omics analysis.Frontiers in molecular biosciences · 2022Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Initiation of T cell receptor (TCR) signaling involves the activation of the tyrosine kinase LCK; however, it is currently unclear how LCK is recruited and activated. Here, we have identified the membrane protein CD146 as an essential member of the TCR network for LCK activation. CD146 deficiency in T cells substantially impaired thymocyte development and peripheral activation, both of which depend on TCR signaling. CD146 was found to directly interact with the SH3 domain of coreceptor-free LCK via its cytoplasmic domain. Interestingly, we found CD146 to be present in both monomeric and dimeric forms in T cells, with the dimerized form increasing after TCR ligation. Increased dimerized CD146 recruited LCK and promoted LCK autophosphorylation. In tumor models, CD146 deficiency dramatically impaired the antitumor response of T cells. Together, our data reveal an LCK activation mechanism for TCR initiation. We also underscore a rational intervention based on CD146 for tumor immunotherapy.
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Registered trials
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.