ArticleThe Journal of clinical investigation2022
CD200 ectodomain shedding into the tumor microenvironment leads to NK cell dysfunction and apoptosis.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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The trial behind it
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Who cites it
37 citing papers in PubMed, 42 citations in OpenAlex.
- Ucenprubart is an agonistic antibody to CD200R with the potential to treat inflammatory skin disease: preclinical development and a phase 1 clinical study.Nature communications · 2025Trial
- Radiation-induced CD200Cellular & molecular immunology · 2026Article
- Plasma proteomics improves thrombosis prediction in patients with cancer and identifies targetable IL-17-driven endothelial activation.Science translational medicine · 2026Article
- Targeting noncanonical nuclear factor kappa B signalling in CYLD cutaneous syndrome by selective inhibition of IκB kinase alpha.The British journal of dermatology · 2026Article
- Increased soluble CD200 in serum of SLE patients does not reflect disease activity or affect CD200R1 function in T cells.Arthritis research & therapy · 2026Article
- Immune Niche Formation Reveals Mechanisms of Tumor Dormancy and Targeting Opportunities.Research square · 2026Article
- CD200 expression predicts poor prognosis in neuroblastoma: a potential biomarker for treatment stratification-a retrospective cohort study.Pediatric surgery international · 2026Article
- Insights into ectodomain shedding as a novel target in natural killer cell-based immunotherapy for cancer.Frontiers in immunology · 2026Review
- Dual targeting of CD244 and CD2 by a viral-immunoevasin-guided engineered CD48-Fc mutant for T- and NK-cell modulation.Frontiers in immunology · 2026Article
- CD200-CD200R as a myeloid immune checkpoint in solid tumors: mechanisms, context-dependent functions, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Macrophage phagocytosis checkpoints in DLBCL immunotherapy: an evidence-maturity framework from CD47 to CD200.Frontiers in oncology · 2026Review
- COL4A1 Promotes Gastric Cancer Progression by Regulating Tumor Invasion, Tumor Microenvironment and Drug Sensitivity.Current medicinal chemistry · 2026Article
- Proteomic Portrait of Degranulation Program in Human Circulating Neutrophils Upon Multi-Inflammatory and Infectious Activation.Molecular & cellular proteomics : MCP · 2026Article
- Immunopathogenesis and Therapeutic Implications in Basal Cell Carcinoma: Current Concepts and Future Directions.Medicina (Kaunas, Lithuania) · 2025Review
- CD200R blockade enhances anti-tumor immunity by unleashing NK and CD8Acta pharmacologica Sinica · 2025Article
- Natural Killer Cell Activation Signature Identifies Cyclin B1/CDK1 as a Druggable Target to Overcome Natural Killer Cell Dysfunction and Tumor Invasiveness in Melanoma.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Immune Niche Formation in Engineered Mouse Models Reveals Mechanisms of Tumor Dormancy.bioRxiv : the preprint server for biology · 2025Article
- Clinical Utility of Serum sCD200/sCD200R Ratios in Predicting Current Activity of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.Journal of clinical medicine · 2025Article
- Apoptotic Caspases-3 and -7 Cleave Extracellular Domains of Membrane-Bound Proteins from MDA-MB-231 Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Cancer-associated fibroblast-derived MMP11 promotes tumor progression in pancreatic cancer.Cancer science · 2025Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
Abstract
The basis of immune evasion, a hallmark of cancer, can differ even when cancers arise from one cell type such as in the human skin keratinocyte carcinomas: basal and squamous cell carcinoma. Here we showed that the basal cell carcinoma tumor-initiating cell surface protein CD200, through ectodomain shedding, was responsible for the near absence of NK cells within the basal cell carcinoma tumor microenvironment. In situ, CD200 underwent ectodomain shedding by metalloproteinases MMP3 and MMP11, which released biologically active soluble CD200 into the basal cell carcinoma microenvironment. CD200 bound its cognate receptor on NK cells to suppress MAPK pathway signaling that in turn blocked indirect (IFN-γ release) and direct cell killing. In addition, reduced ERK phosphorylation relinquished negative regulation of PPARγ-regulated gene transcription and led to membrane accumulation of the Fas/FADD death receptor and its ligand, FasL, which resulted in activation-induced apoptosis. Blocking CD200 inhibition of MAPK or PPARγ signaling restored NK cell survival and tumor cell killing, with relevance to many cancer types. Our results thus uncover a paradigm for CD200 as a potentially novel and targetable NK cell-specific immune checkpoint, which is responsible for NK cell-associated poor outcomes in many cancers.
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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 OpenQuestion graph.