ArticlePloS one2013
Combining antiangiogenic therapy with adoptive cell immunotherapy exerts better antitumor effects in non-small cell lung cancer models.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Anti-Angiogenic Agents Combined with Immunotherapy for Advanced Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.Combinatorial chemistry & high throughput screening · 2024Pooled it
- XELOX (capecitabine plus oxaliplatin) plus bevacizumab (anti-VEGF-A antibody) with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer: a multicenter, open-label, randomized, controlled, phase 3 trial.Signal transduction and targeted therapy · 2024Trial
- Immune response, safety, and survival and quality of life outcomes for advanced colorectal cancer patients treated with dendritic cell vaccine and cytokine-induced killer cell therapy.BioMed research international · 2014Trial
- VEGFR2 blockade converts thermally ablative focused ultrasound into a potent driver of T cell-dependent anti-tumor immunity.bioRxiv : the preprint server for biology · 2025Article
- Histotripsy-Focused Ultrasound Treatment Abrogates Tumor Hypoxia Responses and Stimulates Antitumor Immune Responses in Melanoma.Molecular cancer therapeutics · 2025Article
- Prospects for Treatment of Lung Cancer Using Activated Lymphocytes Combined with Other Anti-Cancer Modalities.Advances in respiratory medicine · 2024Review
- Pericytes recruited by CCL28 promote vascular normalization after anti-angiogenesis therapy through RA/RXRA/ANGPT1 pathway in lung adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2024Article
- Progress of immune checkpoint inhibitors therapy for non-small cell lung cancer with liver metastases.British journal of cancer · 2024Review
- Phase 2 Trial of Nivolumab and Ramucirumab for Relapsed Mesothelioma: HCRN-LUN15-299.JTO clinical and research reports · 2023Article
- Current status and future of anti-angiogenic drugs in lung cancer.Clinical and experimental medicine · 2023Review
- Immunotherapies targeting tumor vasculature: challenges and opportunities.Frontiers in immunology · 2023Review
- Clinical Efficacy of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer Patients with Liver Metastases: A Network Meta-Analysis of Nine Randomized Controlled Trials.Cancer research and treatment · 2022Article
- Cancer combination therapies by angiogenesis inhibitors; a comprehensive review.Cell communication and signaling : CCS · 2022Review
- Ang2-Targeted Combination Therapy for Cancer Treatment.Frontiers in immunology · 2022Review
- VEGF/VEGFR-Targeted Therapy and Immunotherapy in Non-small Cell Lung Cancer: Targeting the Tumor Microenvironment.International journal of biological sciences · 2022Review
- The Research Progress of Antiangiogenic Therapy, Immune Therapy and Tumor Microenvironment.Frontiers in immunology · 2022Review
- Thymidylate synthase drives the phenotypes of epithelial-to-mesenchymal transition in non-small cell lung cancer.British journal of cancer · 2021Article
- The Combination of Immune Checkpoint Blockade and Angiogenesis Inhibitors in the Treatment of Advanced Non-Small Cell Lung Cancer.Frontiers in immunology · 2021Review
- Potential Therapeutic Strategies for Lung and Breast Cancers through Understanding the Anti-Angiogenesis Resistance Mechanisms.International journal of molecular sciences · 2020Review
- A Window of Opportunity: Targeting Cancer Endothelium to Enhance Immunotherapy.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionCytokine-induced killer cells (CIK cells) are a heterogeneous subset of ex-vivo expanded T lymphocytes which are characterized with a MHC-unrestricted tumor-killing activity and a mixed T-NK phenotype. Adoptive CIK cells transfer, one of the adoptive immunotherapy represents a promising nontoxic anticancer therapy. However, in clinical studies, the therapeutic activity of adoptive CIK cells transfer is not as efficient as anticipated. Possible explanations are that abnormal tumor vasculature and hypoxic tumor microenvironment could impede the infiltration and efficacy of lymphocytes. We hypothesized that antiangiogenesis therapy could improve the antitumor activity of CIK cells by normalizing tumor vasculature and modulating hypoxic tumor microenvironment.
methodsWe combined recombinant human endostatin (rh-endostatin) and CIK cells in the treatment of lung carcinoma murine models. Intravital microscopy, dynamic contrast enhanced magnetic resonance imaging, immunohistochemistry, and flow cytometry were used to investigate the tumor vasculature and hypoxic microenvironment as well as the infiltration of immune cells.
resultsOur results indicated that rh-endostatin synergized with adoptive CIK cells transfer to inhibit the growth of lung carcinoma. We found that rh-endostatin normalized tumor vasculature and reduced hypoxic area in the tumor microenvironment. Hypoxia significantly inhibited the proliferation, cytotoxicity and migration of CIK cells in vitro and impeded the homing of CIK cells into tumor parenchyma ex vivo. Furthermore, we found that treatment with rh-endostatin significantly increased the homing of CIK cells and decreased the accumulation of suppressive immune cells in the tumor tissue. In addition, combination therapy produced higher level of tumor-infiltration lymphocytes compared with other treatments.
conclusionsOur results demonstrate that rh-endostatin improves the therapeutic effect of adoptive CIK cells therapy against lung carcinomas and unmask the mechanisms of the synergistic antitumor efficacy, providing a new rationale for combining antiangiogenesis therapy with immunotherapy in the treatment of lung cancer.
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Registered trials
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