ArticleProceedings of the National Academy of Sciences of the United States of America2018
CD226 regulates natural killer cell antitumor responses via phosphorylation-mediated inactivation of transcription factor FOXO1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 62 citations in OpenAlex.
- Adjuvant nivolumab, capecitabine or the combination in patients with residual triple-negative breast cancer: the OXEL randomized phase II study.Nature communications · 2024Trial
- Gadd45α silencing alleviates cerebral ischemia-reperfusion injury by suppressing FOXO1 signaling.Scientific reports · 2026Article
- Agent-based modeling of cellular dynamics in adoptive cell therapy.Communications biology · 2026Article
- Glucocorticoid Receptor Activation Reprograms NK Cells to Drive AREG-Mediated Immunosuppression: A Pan-Cancer Role for AREG.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Therapeutic targeting of cell death-immune crosstalk in cancer to rewire the tumor immune microenvironment.Molecular cancer · 2025Review
- Structure-guided engineering of CD112 receptor variants for optimized immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Unlocking new frontiers: novel immune targets for next-generation cancer immunotherapy.Korean journal of clinical oncology · 2025Review
- The Immune Regulatory Functions of CD226 and Its Implications in Immune-Mediated Diseases.Biomolecules · 2025Review
- Inhibition of CD226 co-stimulation suppresses diabetes development in the NOD mouse by augmenting regulatory T cells and diminishing effector T cell function.Diabetologia · 2025Article
- Spatial and Single-Cell Analyses Reveal Heterogeneity of DNAM-1 Receptor-Ligand Interactions That Instructs Intratumoral γδT-cell Activity.Cancer research · 2025Article
- A 41-marker 37-color full spectrum flow cytometry panel for the deep immunophenotyping of human peripheral and liver natural killer cells.Frontiers in immunology · 2025Article
- Turning Cancer Immunotherapy to the Emerging Immune Checkpoint TIGIT: Will This Break Through the Limitations of the Legacy Approach?Vaccines · 2024Article
- Comprehensive snapshots of natural killer cells functions, signaling, molecular mechanisms and clinical utilization.Signal transduction and targeted therapy · 2024Review
- Revisiting T-cell adhesion molecules as potential targets for cancer immunotherapy: CD226 and CD2.Experimental & molecular medicine · 2024Review
- Inhibition of CD226 Co-Stimulation Suppresses Diabetes Development in the NOD Mouse by Augmenting Tregs and Diminishing Effector T Cell Function.bioRxiv : the preprint server for biology · 2024Article
- Dysfunctional natural killer cells can be reprogrammed to regain anti-tumor activity.The EMBO journal · 2024Article
- Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities.Signal transduction and targeted therapy · 2024Review
- Immune Regulation and Immune Therapy in Melanoma: Review with Emphasis on CD155 Signalling.Cancers · 2024Review
- Current Landscape of Cancer Immunotherapy: Harnessing the Immune Arsenal to Overcome Immune Evasion.Biology · 2024Review
- Single-cell RNA sequencing unveils tumor heterogeneity and immune microenvironment between subungual and plantar melanoma.Scientific reports · 2024Article
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural killer (NK) cell recognition of tumor cells is mediated through activating receptors such as CD226, with suppression of effector functions often controlled by negative regulatory transcription factors such as FOXO1. Here we show that CD226 regulation of NK cell cytotoxicity is facilitated through inactivation of FOXO1. Gene-expression analysis of NK cells isolated from syngeneic tumors grown in wild-type or CD226-deficient mice revealed dysregulated expression of FOXO1-regulated genes in the absence of CD226. In vitro cytotoxicity and stimulation assays demonstrated that CD226 is required for optimal killing of tumor target cells, with engagement of its ligand CD155 resulting in phosphorylation of FOXO1. CD226 deficiency or anti-CD226 antibody blockade impaired cytotoxicity with concomitant compromised inactivation of FOXO1. Furthermore, inhibitors of FOXO1 phosphorylation abrogated CD226-mediated signaling and effector responses. These results define a pathway by which CD226 exerts control of NK cell responses against tumors.
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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.