ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Anlotinib Induces a T Cell-Inflamed Tumor Microenvironment by Facilitating Vessel Normalization and Enhances the Efficacy of PD-1 Checkpoint Blockade in Neuroblastoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04842526 (Efficacy and Safety of Anlotinib, Irinotecan and Temozolomide in the Treatment of Refractory or Recurrent Neuroblastoma in Children), which is not on this map. Cited by 114 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Efficacy and Safety of Anlotinib, Irinotecan and Temozolomide in the Treatment of Refractory or Recurrent Neuroblastoma in Children: an Open, Single Arm, Single Center, Phase II Clinical Study
Who cites it
114 citing papers in PubMed, 2 syntheses or guidelines pooled it, 139 citations in OpenAlex.
- Efficacy and safety of anlotinib combined with immune checkpoint inhibitors in the treatment of extensive-stage small cell lung cancer: a meta-analysis based on real-world data.BMC pulmonary medicine · 2025Pooled it
- Efficacy and safety of immunotherapy or antiangiogenic agent-based treatment strategies versus chemotherapy as first-line treatment for extensive-stage small cell lung cancer: a network meta-analysis.Frontiers in pharmacology · 2025Pooled it
- Efficacy and biomarker exploration of anlotinib plus penpulimab in second-line ES-SCLC: Results from the phase 2 ALTER-L041 trial.Cell reports. Medicine · 2026Trial
- Sintilimab plus Bevacizumab biosimilar IBI305 and chemotherapy as a first-line treatment in advanced gastric or gastroesophageal junction adenocarcinoma (SBAGA): a single-arm, phase Ib/II study.Nature communications · 2026Trial
- Anlotinib combined with neoadjuvant chemotherapy for HR+/HER2- breast cancer (ACNTBC): a prospective, single-arm, single-center phase II clinical study with real-world validation.Signal transduction and targeted therapy · 2026Trial
- Preliminary results from a phase II trial of spatially fractionated radiotherapy combined with immunotherapy and anti-angiogenic therapy in patients with bulky solid tumors: early evidence of promising efficacy and favorable safety.Radiation oncology (London, England) · 2026Trial
- Perioperative penpulimab-based combination therapy in patients with resectable non-small cell lung cancer (ALTER-L043): an open-label, multicenter, randomized, phase II trial.Signal transduction and targeted therapy · 2026Trial
- Sitravatinib plus tislelizumab in locally recurrent or metastatic triple-negative breast cancer: a multi-cohort, single-arm, phase II clinical trial (SPARK Trial).Molecular cancer · 2025Trial
- Efficacy analysis of TACE in combination with anlotinib and sintilimab in the treatment of unresectable hepatocellular carcinoma.Scientific reports · 2025Trial
- Anlotinib plus camrelizumab and chemotherapy as first-line treatment in patients with advanced esophageal squamous cell carcinoma.Scientific reports · 2025Trial
- Anlotinib Plus Docetaxel is Promising in Advanced NSCLC Progressing on First-Line Immunotherapy: A Pooled Analysis of Two Randomized Trials.Advances in therapy · 2025Trial
- Benmelstobart plus anlotinib and chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: A phase 2 study.Cell reports. Medicine · 2025Trial
- Anlotinib combined with benmelstobart as a chemo-free first-line treatment in advanced esophageal squamous cell carcinoma: an exploratory multicenter, single-arm phase II clinical trial.Molecular cancer · 2025Trial
- Anlotinib plus chemotherapy as a first-line treatment for gastrointestinal cancer patients with unresectable liver metastases: a multicohort, multicenter, exploratory trial.Signal transduction and targeted therapy · 2024Trial
- First-line benmelstobart plus anlotinib and chemotherapy in advanced or metastatic/recurrent esophageal squamous cell carcinoma: a multi-center phase 2 study.Signal transduction and targeted therapy · 2024Trial
- Perioperative sintilimab and neoadjuvant anlotinib plus chemotherapy for resectable non-small-cell lung cancer: a multicentre, open-label, single-arm, phase 2 trial (TD-NeoFOUR trial).Signal transduction and targeted therapy · 2024Trial
- Nivolumab plus anlotinib hydrochloride in advanced gastric adenocarcinoma and esophageal squamous cell carcinoma: the phase II OASIS trial.Nature communications · 2024Trial
- Enhancement of anti-PD-L1 antibody plus anlotinib efficacy due to downregulation of PD-L1 in the micro-conduit endothelium within the tumor: a randomized double-blind trial.Cancer biology & medicine · 2024Trial
- A phase Ib/II study of cadonilimab (PD-1/CTLA-4 bispecific antibody) plus anlotinib as first-line treatment in patients with advanced non-small cell lung cancer.British journal of cancer · 2024Trial
- Integrated Genomic and Proteomic Analysis Reveals T-B Lymphocyte Signatures in the MYCN Driven "Immune Desert" of Specific Neuroblastoma Subtypes.CNS neuroscience & therapeutics · 2026Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
purposeAnlotinib has achieved good results in clinical trials of a variety of cancers. However, the effects of anlotinib on the tumor microenvironment (TME) and systemic immunity have not been reported. There is an urgent need to identify the underlying mechanism to reveal new opportunities for its application in neuroblastoma (NB) and other cancers. Understanding the mechanism will hopefully achieve the goal of using the same method to treat different cancers. EXPERIMENTAL
designThis study used bioinformatics, NB syngeneic mouse models, flow cytometry, RNA-seq, and immunofluorescence staining to explore the mechanisms of anlotinib on the TME, and further explored anlotinib-containing combination treatment strategies.
resultsWe proved that anlotinib facilitates tumor vessel normalization at least partially through CD4+ T cells, reprograms the immunosuppressive TME into an immunostimulatory TME, significantly inhibits tumor growth, and effectively prevents systemic immunosuppression. Moreover, the combination of anlotinib with a PD-1 checkpoint inhibitor counteracts the immunosuppression caused by the upregulation of PD-L1 after monotherapy, extends the period of vascular normalization, and finally induces NB regression.
conclusionsTo our knowledge, this study is the first to dynamically evaluate the effect of a multitarget antiangiogenic tyrosine kinase inhibitor on the TME. These findings have very important clinical value in guiding the testing of related drugs in NB and other cancers. Based on these findings, we are conducting a phase II clinical study (NCT04842526) on the efficacy and safety of anlotinib, irinotecan, and temozolomide in the treatment of refractory or relapsed NB, and hopefully we will observe patient benefit.
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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.