ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
DLK1: a novel target for immunotherapeutic remodeling of the tumor blood vasculature.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
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Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 39 citations in OpenAlex.
- Immunosuppressive roles of pericytes in cancer disease: insights from a systematic review and meta-analysis.Journal of translational medicine · 2026Pooled it
- The Role of Chemokine Receptor CXCR3 and Its Ligands in Renal Cell Carcinoma.International journal of molecular sciences · 2020Pooled it
- Dendritic cell vaccines targeting tumor blood vessel antigens in combination with dasatinib induce therapeutic immune responses in patients with checkpoint-refractory advanced melanoma.Journal for immunotherapy of cancer · 2021Trial
- Therapeutic DC vaccination against the vascular antigen DLK1 effectively treats primary triple-negative breast cancer and prevents metastasis.NPJ vaccines · 2026Article
- DLK1: a novel therapeutic target in cancer.Endocrine-related cancer · 2026Review
- Molecular mechanism of Activin receptor inhibition by DLK1.Nature communications · 2025Article
- Silencing YTHDF2 Induces Apoptosis of Neuroblastoma Cells In a Cell Line-Dependent Manner via Regulating the Expression of DLK1.Molecular neurobiology · 2025Article
- Identification of PECAM1 as a Prognostic Biomarker for Lung Adenocarcinoma.Diagnostics (Basel, Switzerland) · 2025Article
- A Phase I, First-In-Human Study of CBA-1205, an Anti-DLK1 Monoclonal Antibody, in Patients With Advanced Solid Tumors.Cancer science · 2025Article
- DLK1 promoted ischemic angiogenesis through notch1 signaling in endothelial progenitor cells.Acta pharmacologica Sinica · 2024Article
- Article
- Review
- Pericytes: jack-of-all-trades in cancer-related inflammation.Frontiers in pharmacology · 2024Review
- Targeting the pericyte antigen DLK1 with an alpha type-1 polarized dendritic cell vaccine results in tumor vascular modulation and protection against colon cancer progression.Frontiers in immunology · 2023Article
- Oncolytic adenovirus promotes vascular normalization and nonclassical tertiary lymphoid structure formation through STING-mediated DC activation.Oncoimmunology · 2022Article
- Model systems in SDHx-related pheochromocytoma/paraganglioma.Cancer metastasis reviews · 2021Review
- Review
- STING agonist-based treatment promotes vascular normalization and tertiary lymphoid structure formation in the therapeutic melanoma microenvironment.Journal for immunotherapy of cancer · 2021Article
- The Emerging Roles of Pericytes in Modulating Tumor Microenvironment.Frontiers in cell and developmental biology · 2021Review
- Activation of Notch signaling by soluble Dll4 decreases vascular permeability via a cAMP/PKA-dependent pathway.American journal of physiology. Heart and circulatory physiology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Tumor blood vessels are frequently inefficient in their design and function, leading to high interstitial fluid pressure, hypoxia, and acidosis in the tumor microenvironment (TME), rendering tumors refractory to the delivery of chemotherapeutic agents and immune effector cells. Here we identified the NOTCH antagonist delta-like 1 homologue (DLK1) as a vascular pericyte-associated antigen expressed in renal cell carcinomas (RCC), but not in normal kidney tissues in mice and humans. Vaccination of mice bearing established RCC against DLK1 led to immune-mediated elimination of DLK1(+) pericytes and to blood vessel normalization (i.e., decreased vascular permeability and intratumoral hypoxia) in the TME, in association with tumor growth suppression. After therapeutic vaccination, tumors displayed increased prevalence of activated VCAM1(+)CD31(+) vascular endothelial cells (VECs) and CXCL10, a type-1 T cell recruiting chemokine, in concert with increased levels of type-1 CD8(+) tumor-infiltrating lymphocytes (TIL). Vaccination against DLK1 also yielded (i) dramatic reductions in Jarid1B(+), CD133(+), and CD44(+) (hypoxia-responsive) stromal cell populations, (ii) enhanced tumor cell apoptosis, and (iii) increased NOTCH signaling in the TME. Coadministration of a γ-secretase inhibitor (N-[N-(3,5-Difluorophenacetyl-l-alanyl)]-(S)-phenylglycine t-butyl ester (DAPT)) that interferes with canonical NOTCH signaling resulted in the partial loss of therapeutic benefits associated with lentivirus encoding full-length murine (lvDLK1)-based vaccination.
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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.