ArticleThe Journal of clinical investigation2023
Angiopoietin-2 blockade suppresses growth of liver metastases from pancreatic neuroendocrine tumors by promoting T cell recruitment.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 12 citations in OpenAlex.
- Conserved Metastatic Cell States and Spatial Immune Microenvironment Remodeling Define Pancreatic Cancer Liver Metastases.bioRxiv : the preprint server for biology · 2026Article
- Adaptive resistance in cancer immunotherapy.Cellular & molecular immunology · 2026Review
- A novel prognostic model based on MVIRGs identifies ANGPT2 as a key target driving the malignant progression of HCC.Biological procedures online · 2026Article
- Dehydrocorydaline Exerts Anti-Pancreatic Cancer Effects Through the PI3K/Akt/mTOR Pathway.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Immunosuppressive Environment of Pancreatic NENs-A Review.Biomedicines · 2026Review
- Angiopoietin-2 aggravates Alzheimer's disease by promoting blood-brain barrier dysfunction and neuroinflammation.Cell reports · 2026Article
- TGFBI deficiency facilitates tumor associated macrophages M2 polarization and angiogenesis to promote pancreatic neuroendocrine neoplasms progression.Cancer cell international · 2026Article
- Dual targeting of CDK4/6 and CDK7 augments tumor response and antitumor immunity in breast cancer models.The Journal of clinical investigation · 2025Article
- The role of immune cells phenotype in neuroendocrine tumors development.Discover oncology · 2025Article
- Establishment and Validation of the Diagnostic Value of Oligodendrocyterelated Genes in Alzheimer's Disease.CNS & neurological disorders drug targets · 2025Article
- IFN-γ-mediated suppression of ANGPT2-Tie2 in endothelial cells facilitates tumor vascular normalization during immunotherapy.Frontiers in immunology · 2025Article
- Prognostic significance and immune microenvironment infiltration patterns of hypoxia and endoplasmic reticulum stress-related genes in gastric cancer.Frontiers in oncology · 2025Article
- Milestones in tumor vascularization and its therapeutic targeting.Nature cancer · 2024Review
- Targeting vascular normalization: a promising strategy to improve immune-vascular crosstalk in cancer immunotherapy.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Improving the management of metastasis in pancreatic neuroendocrine tumors (PanNETs) is critical, as nearly half of patients with PanNETs present with liver metastases, and this accounts for the majority of patient mortality. We identified angiopoietin-2 (ANGPT2) as one of the most upregulated angiogenic factors in RNA-Seq data from human PanNET liver metastases and found that higher ANGPT2 expression correlated with poor survival rates. Immunohistochemical staining revealed that ANGPT2 was localized to the endothelial cells of blood vessels in PanNET liver metastases. We observed an association between the upregulation of endothelial ANGPT2 and liver metastatic progression in both patients and transgenic mouse models of PanNETs. In human and mouse PanNET liver metastases, ANGPT2 upregulation coincided with poor T cell infiltration, indicative of an immunosuppressive tumor microenvironment. Notably, both pharmacologic inhibition and genetic deletion of ANGPT2 in PanNET mouse models slowed the growth of PanNET liver metastases. Furthermore, pharmacologic inhibition of ANGPT2 promoted T cell infiltration and activation in liver metastases, improving the survival of mice with metastatic PanNETs. These changes were accompanied by reduced plasma leakage and improved vascular integrity in metastases. Together, these findings suggest that ANGPT2 blockade may be an effective strategy for promoting T cell infiltration and immunostimulatory reprogramming to reduce the growth of liver metastases in PanNETs.
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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.