ArticleJournal for immunotherapy of cancer2020
Multifaceted effects of soluble human CD6 in experimental cancer models.
Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 11 citations in OpenAlex.
- Targeting CD6 in solid tumors: safety, early efficacy, and mechanistic insights from a proof-of-concept trial of itolizumab.Journal for immunotherapy of cancer · 2026Article
- Defining the Functional Role and Potential as an Immunotherapeutic Target of ALCAM in Neuroblastoma.Molecular cancer therapeutics · 2026Article
- Itolizumab regulates activating and inhibitory signals on effector cells, improving their cytotoxicity against CD318+ tumor cell lines.Frontiers in immunology · 2025Article
- Inference and analysis of cell-cell communication of non-myeloid circulating cells in late sepsis based on single-cell RNA-seq.IET systems biology · 2024Article
- Ligands of CD6: roles in the pathogenesis and treatment of cancer.Frontiers in immunology · 2024Review
- CD6 and Its Interacting Partners: Newcomers to the Block of Cancer Immunotherapies.International journal of molecular sciences · 2023Review
- Advanced immunotherapies for glioblastoma: tumor neoantigen vaccines in combination with immunomodulators.Acta neuropathologica communications · 2023Review
- Molecular characterization of ESR1 variants in breast cancer.Breast cancer research and treatment · 2022Article
- Gene variation impact on prostate cancer progression: Lymphocyte modulator, activation, and cell adhesion gene variant contribution.The Prostate · 2022Article
- CD6 is a target for cancer immunotherapy.JCI insight · 2021Article
- Silica Induction of Diverse Inflammatory Proteome in Lungs of Lupus-Prone Mice Quelled by Dietary Docosahexaenoic Acid Supplementation.Frontiers in immunology · 2021Article
- Soluble CD5 and CD6: Lymphocytic Class I Scavenger Receptors as Immunotherapeutic Agents.Cells · 2020Review
- Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundCD6 is a lymphocyte surface co-receptor physically associated with the T-cell receptor (TCR)/CD3 complex at the center of the immunological synapse. There, CD6 assists in cell-to-cell contact stabilization and modulation of activation/differentiation events through interaction with CD166/ALCAM (activated leukocyte cell adhesion molecule), its main reported ligand. While accumulating evidence is attracting new interest on targeting CD6 for therapeutic purposes in autoimmune disorders, little is known on its potential in cancer. In an attempt to elucidate the in vivo relevance of blocking CD6-mediated interactions in health and disease, we explored the consequences of expressing high circulating levels of a soluble form CD6 (sCD6) as a decoy receptor.
methodsHigh sCD6 serum levels were achieved by using transgenic C57BL/6 mice expressing human sCD6 under the control of lymphoid-specific transcriptional elements (shCD6LckEμTg) or wild type either transduced with hepatotropic adeno-associated virus coding for mouse sCD6 or undergoing repeated infusions of recombinant human sCD6 protein. Characterization of sCD6-induced changes was performed by ex vivo flow cytometry and functional analyses of mouse lymphoid organ cells. The in vivo relevance of those changes was explored by challenging mice with subcutaneous or metastatic tumors induced by syngeneic cancer cells of different lineage origins.
resultsThrough a combination of in vitro and in vivo studies, we show that circulating sCD6 expression induces defective regulatory T cell (Treg) generation and function, decreased CD166/ALCAM-mediated tumor cell proliferation/migration and impaired galectin-induced T-cell apoptosis, supporting the fact that sCD6 modulates antitumor lymphocyte effector function and tumorigenesis. Accordingly, sCD6 expression in vivo resulted in delayed subcutaneous tumor growth and/or reduced metastasis on challenge of mice with syngeneic cancer cells.
conclusionsEvidence is provided for the disruption of CD6 receptor-ligand interactions as a feasible immunomodulatory approach in cancer.
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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 OpenQuestion graph.