ArticleCancer science2023
Combination therapy of DKK1 inhibition and NKG2D chimeric antigen receptor T cells for the treatment of gastric cancer.
Article in Cancer science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- The evolution of cellular-based immunotherapy in the treatment of gastric cancer: an overview of clinical trials.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- The Dickkopf-1 (DKK1) Dichotomy in Oncology: New Insights on Tumor Progression and Immune Regulation.International journal of molecular sciences · 2026Review
- Targeting NKG2D/NKG2DL axis in cancer immunotherapy: mechanisms and therapeutic applications.Journal of translational medicine · 2026Review
- NKG2D CAR-T cells for solid tumor immunotherapy: advances, challenges, and future directions.Frontiers in immunology · 2026Review
- The Metabolic Regulation of the NKG2D-Positive NK and T Cells and Their Role in Disease Progression.Biomolecules · 2025Review
- ULBP2 CAR-T cells enhance gastric cancer immunotherapy by inhibiting CAF activation.Cell death & disease · 2025Article
- Research progress on monocyte/macrophage in the development of gastric cancer.Future oncology (London, England) · 2025Review
- New approaches of chimeric antigen receptor (CAR)-immune cell-based therapy in gastric cancer; highlight CAR-T and CAR-NK.Functional & integrative genomics · 2025Review
- Stroma-derived Dickkopf-1 contributes to the suppression of NK cell cytotoxicity in breast cancer.Nature communications · 2025Article
- DKK1 and Its Receptors in Esophageal Adenocarcinoma: A Promising Molecular Target.Diagnostics (Basel, Switzerland) · 2025Review
- Harnessing NKG2D CAR-T cells with radiotherapy: a novel approach for esophageal squamous cell carcinoma treatment.Frontiers in immunology · 2025Article
- Current Advances and Challenges in CAR-T Therapy for Hematological and Solid Tumors.ImmunoTargets and therapy · 2025Review
- Designs of NKG2D-based immunotherapeutics for cancer.Frontiers in immunology · 2025Review
- Molecular Mechanism for Malignant Progression of Gastric Cancer Within the Tumor Microenvironment.International journal of molecular sciences · 2024Review
- Identification of XD23 as a potent inhibitor of osteosarcoma via downregulation of DKK1 and activation of the WNT/β-catenin pathway.iScience · 2024Article
- Clinical significance of peripheral blood immune cells in patients with gastric cancer after surgery.World journal of gastrointestinal surgery · 2024Article
- Exploring the immune escape mechanisms in gastric cancer patients based on the deep AI algorithms and single-cell sequencing analysis.Journal of cellular and molecular medicine · 2024Article
- Combination therapy of DKK1 inhibition and NKG2D chimeric antigen receptor T cells for the treatment of gastric cancer.Cancer science · 2023Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Despite the successful application of chimeric antigen receptor (CAR)-T cell therapy in hematological malignancies, the treatment efficacy in solid tumors remains unsatisfactory, largely due to the highly immunosuppressive tumor microenvironment and low density of specific tumor antigens. Natural killer group 2 member D (NKG2D) CAR-T cells have shown promising treatment effects on several cancers such as lymphoma and multiple myeloma. However, the application and efficacy of NKG2D-CAR-T cells in gastric cancer (GC) still needs further exploration. This study identified a novel combination immunotherapy strategy with Dickkopf-1 (DKK1) inhibition and NKG2D-CAR-T cells, exerting synergistic and superior antitumor effect in GC. We show that the baseline expression of NKG2D ligands (NKG2DLs) is at low levels in GC tissues from The Cancer Genome Atlas and multiple GC cell lines including NCI-N87, MGC803, HGC27, MKN45, SGC7901, NUGC4, and AGS. In addition, DKK1 inhibition by WAY-262611 reverses the suppressive tumor immune microenvironment (TIME) and upregulates NKG2DL expression levels in both GC cell lines and GC tissues from a xenograft NCG mouse model. DKK1 inhibition in GC cells markedly improves the immune-activating and tumor-killing ability of NKG2D-CAR-T cells as shown by cytotoxicity assays in vitro. Moreover, the combination therapy of NKG2D-CAR-T and WAY-262611 triggers superior antitumor effects in vivo in a xenograft NCG mouse model. In sum, our study reveals the role of DKK1 in remodeling GC TIME and regulating the expression levels of NKG2DLs in GC. We also provide a promising treatment strategy of combining DKK1 inhibition with NKG2D-CAR-T cell therapy, which could bring new breakthroughs for GC 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 OpenQuestion graph.