ArticleCancer research2011
mTOR kinase inhibitor AZD8055 enhances the immunotherapeutic activity of an agonist CD40 antibody in cancer treatment.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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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.
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Who cites it
52 citing papers in PubMed, 81 citations in OpenAlex.
- Inhibition of mTOR Signaling and Clinical Activity of Rapamycin in Head and Neck Cancer in a Window of Opportunity Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- Polymeric Materials in Cancer Immunotherapy: Advances, Challenges, and Future Directions.Polymer science & technology (Washington, D.C.) · 2026Review
- Ole-4, a novel synthetic derivative of Oleuropein, enhances antitumor immunity and modulates kinase activity-dependent signaling.Journal of translational medicine · 2026Article
- United multi-omics and machine learning refine regulatory T cell-defined hepatocellular carcinoma subtypes.iScience · 2026Article
- Natural Killer Cell-Mediated Antitumor Immunity: Molecular Mechanisms and Clinical Applications.MedComm · 2025Review
- Immune Evasion Mechanism Mediated by ITPRIPL1 and Its Prognostic Implications in Glioma.Brain and behavior · 2025Article
- Identification and verification of aging-related lncRNAs for prognosis prediction and immune microenvironment in patients with head and neck squamous carcinoma.Oncology research · 2023Article
- Targeting mTOR as a Cancer Therapy: Recent Advances in Natural Bioactive Compounds and Immunotherapy.Cancers · 2022Review
- Targeting PI3K/Akt signal transduction for cancer therapy.Signal transduction and targeted therapy · 2021Review
- Combined targeted therapy and immunotherapy for cancer treatment.World journal of clinical cases · 2021Review
- A systems-level study reveals host-targeted repurposable drugs against SARS-CoV-2 infection.Molecular systems biology · 2021Article
- Review
- Nanomaterials Enhance the Immunomodulatory Effect of Molecular Targeted Therapy.International journal of nanomedicine · 2021Review
- Searching for the real function of mTOR signaling in the regulation of PD-L1 expression.Translational oncology · 2020Review
- Regulation of RLR-Mediated Antiviral Responses of Human Dendritic Cells by mTOR.Frontiers in immunology · 2020Article
- Response of metastatic mouse invasive lobular carcinoma to mTOR inhibition is partly mediated by the adaptive immune system.Oncoimmunology · 2020Article
- Immune Modulation of Head and Neck Squamous Cell Carcinoma and the Tumor Microenvironment by Conventional Therapeutics.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Review
- Deptor Is a Novel Target of Wnt/β-Catenin/c-Myc and Contributes to Colorectal Cancer Cell Growth.Cancer research · 2018Article
- Article
- Tumor microenvironment confers mTOR inhibitor resistance in invasive intestinal adenocarcinoma.Oncogene · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
mTOR is a central mediator of cancer cell growth, but it also directs immune cell differentiation and function. On this basis, we had explored the hypothesis that mTOR inhibition can enhance cancer immunotherapy. Here, we report that a combination of αCD40 agonistic antibody and the ATP-competitive mTOR kinase inhibitory drug AZD8055 elicited synergistic antitumor responses in a model of metastatic renal cell carcinoma. In contrast to the well-established mTOR inhibitor rapamycin, AZD8055 increased the infiltration, activation, and proliferation of CD8(+) T cells and natural killer cells in liver metastatic foci when combined with the CD40 agonist. AZD8055/αCD40-treated mice also display an increased incidence of matured macrophages and dendritic cells compared with that achieved in mice by αCD40 or AZD8055 treatment alone. We found that the combination treatment also increased macrophage production of TNFα, which played an indispensable role in activation of the observed antitumor immune response. Levels of Th1 cytokines, including interleukin 12, IFN-γ, TNFα, and the Th1-associated chemokines RANTES, MIG, and IP-10 were each elevated significantly in the livers of mice treated with the combinatorial therapy versus individual treatments. Notably, the AZD8055/αCD40-induced antitumor response was abolished in IFN-γ(-/-) and CD40(-/-) mice, establishing the reliance of the combination therapy on host IFN-γ and CD40 expression. Our findings offer a preclinical proof of concept that, unlike rapamycin, the ATP-competitive mTOR kinase inhibitor AZD8055 can contribute with αCD40 treatment to trigger a restructuring of the tumor immune microenvironment to trigger regressions of an established metastatic cancer.
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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.