ArticleCancer immunology, immunotherapy : CII2020
Anti-angiogenesis therapy overcomes the innate resistance to PD-1/PD-L1 blockade in VEGFA-overexpressed mouse tumor models.
Article in Cancer immunology, immunotherapy : CII, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.
- Biomarkers and factors in small cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis.Cancer medicine · 2023Pooled it
- Safety and efficacy of transarterial chemoembolization combined with tyrosine kinase inhibitors and camrelizumab in the treatment of patients with advanced unresectable hepatocellular carcinoma.Frontiers in immunology · 2023Trial
- Mechanisms and advances of drug resistance in colorectal cancer: A systematic overview of multi-layered regulatory networks.Translational oncology · 2026Review
- Synergistic Anticancer Effects of Apatinib and PD-L1 Inhibition in Breast Cancer.Journal of mammary gland biology and neoplasia · 2026Article
- Naringenin: A potential therapeutic agent for modulating angiogenesis and immune response in hepatocellular carcinoma.Journal of pharmaceutical analysis · 2025Article
- Research progress of anti-angiogenic therapy combined with immunotherapy and radiotherapy for the treatment of brain metastases in non-small cell lung cancer (Review).Oncology letters · 2025Review
- Serum proteomics reveals survival-associated biomarkers in pancreatic cancer patients treated with chemoimmunotherapy.iScience · 2025Article
- A comprehensive insights of cancer immunotherapy resistance.Medical oncology (Northwood, London, England) · 2025Review
- T-cell Receptor Repertoire Analysis in the Context of Transarterial Chemoembolization Synergy with Systemic Therapy for Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2025Review
- A Three-agent Regimen for Triple Negative Breast Cancer Treatment.Recent patents on anti-cancer drug discovery · 2025Article
- Camrelizumab combined with gemcitabine and apatinib in treating advanced PD-L1-positive biliary tract cancers.Cancer science · 2025Article
- Article
- Targeting CD47 and Angiogenesis Demonstrates Effective Anti-Tumor Effect in Bladder Cancer.Biomedicines · 2024Article
- Article
- Anlotinib reversed resistance to PD-1 inhibitors in recurrent and metastatic head and neck cancers: a real-world retrospective study.Cancer immunology, immunotherapy : CII · 2024Article
- Efficacy and safety of TACE combined with tyrosine kinase inhibitors and camrelizumab for unresectable hepatocellular carcinoma: A systematic review and meta‑analysis.Oncology letters · 2024Article
- Camptothecin enhances the anti-tumor effect of low-dose apatinib combined with PD-1 inhibitor on hepatocellular carcinoma.Scientific reports · 2024Article
- Senescence drives immunotherapy resistance by inducing an immunosuppressive tumor microenvironment.Nature communications · 2024Article
- YY1: a key regulator inhibits gastric cancer ferroptosis and mediating apatinib-resistance.Cancer cell international · 2024Article
- Narrative review on efficacy and safety of anti-angiogenesis in combination with immunotherapy in the treatment of breast cancer.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2024Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The effectual clinical benefits of immune checkpoint inhibitor (ICI) are hampered by a high rate of innate resistance, and VEGFA may contribute to ICI treatment resistance. In this study, we endeavored to assess the tumor microenvironment (TME) in VEGFA-overexpressed human tumors and mouse tumor models, and to explore whether anti-angiogenesis therapy can overcome the innate resistance to ICI in hyperangiogenesis mouse tumor models and the underlying mechanism. Effect of VEGFA on clinical prognosis and TME was analyzed using TCGA data. The VEGFA-overexpressed mouse breast and colon subcutaneous models were established. PD-1 mAb or apatinib alone and combination therapy were used. Immunohistochemistry and immunofluorescence were used to assess angiogenesis and hypoxia. Flow cytometry, RNA sequencing and MCP-counter were applied to detect tumor immunomicroenvironment. High level of VEGFA mRNA in human tumors is related to poor prognosis and hypoxic, angiogenic and immunosuppressive TME. Upregulation of VEGFA increased the degree of malignancy of tumor cells in vitro and in vivo. VEGFA-overexpressed models were characterized by hypoxic, hyperangiogenic and immunosuppressive TME and indicated innate resistance to ICI. In tumor-bearing mice without VEGFA overexpression, the combination therapy had no synergistic anti-tumor effect compared to monotherapy. However, apatinib alleviated hyperangiogenesis and hypoxia in TME and converted the immunosuppressive TME into an immunostimulatory one in VEGFA-overexpressed tumors. Thus, anti-angiogenesis therapy could improve the efficiency of ICI in VEGFA-overexpressed tumors. Revealing whether there is hypervascularization in tumor tissues may help to clarify the adoption of anti-angiogenesis and ICI combination therapy or ICI monotherapy in cancer treatment.
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Registered trials
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