ArticleOncoimmunology
Zoledronic acid inhibits NFAT and IL-2 signaling pathways in regulatory T cells and diminishes their suppressive function in patients with metastatic cancer.
Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- The Cellular and Mitochondrial Consequences of Mevalonate Pathway Inhibition by Nitrogen-Containing Bisphosphonates: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Metal-modulated T cell antitumor immunity and emerging metalloimmunotherapy.Cancer metastasis reviews · 2025Review
- Protein serine/threonine phosphatases in tumor microenvironment: a vital player and a promising therapeutic target.Theranostics · 2025Review
- Global Publication Trends and Research Hotspots of the Immune System and Osteoporosis: A Bibliometric and Visualization Analysis from 2012 to 2022.Endocrine, metabolic & immune disorders drug targets · 2024Article
- Article
- Adjunctive Zoledronate + IL-2 administrations enhance anti-tuberculosis Vγ2Vδ2 T-effector populations, and improve treatment outcome of multidrug-resistant tuberculosisEmerging microbes & infections · 2022Article
- Interplay between fat cells and immune cells in bone: Impact on malignant progression and therapeutic response.Pharmacology & therapeutics · 2022Review
- Reduced Expression of Natural Killer Cell-Related Activating Receptors by Peripheral Blood Mononuclear Cells from Patients with Breast Cancer and Their Improvement by Zoledronic Acid.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Osteoimmuno-Oncology: Therapeutic Opportunities for Targeting Immune Cells in Bone Metastasis.Cells · 2021Review
- Oestradiol Contributes to Differential Antitumour Effects of Adjuvant Zoledronic Acid Observed Between Pre- and Post-Menopausal Women.Frontiers in endocrinology · 2021Article
- Oestrogen and zoledronic acid driven changes to the bone and immune environments: Potential mechanisms underlying the differential anti-tumour effects of zoledronic acid in pre- and post-menopausal conditions.Journal of bone oncology · 2020Review
- Nonhuman Primate Testing of the Impact of Different Regulatory T Cell Depletion Strategies on Reactivation and Clearance of Latent Simian Immunodeficiency Virus.Journal of virology · 2020Article
- Regulatory T cells in tumor microenvironment: new mechanisms, potential therapeutic strategies and future prospects.Molecular cancer · 2020Review
- Zoledronic acid inhibits the growth of cancer stem cell derived from cervical cancer cell by attenuating their stemness phenotype and inducing apoptosis and cell cycle arrest through the Erk1/2 and Akt pathways.Journal of experimental & clinical cancer research : CR · 2019Article
- Bone-Targeted Agents in Breast Cancer: Do We Now Have All the Answers?Breast cancer : basic and clinical research · 2019Review
- Early Reconstitution of NK and γδ T Cells and Its Implication for the Design of Post-Transplant Immunotherapy.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2018Article
- Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulatory T cells (Treg) suppress anti-tumor immune responses and their infiltration in the tumor microenvironment is associated with inferior prognosis in cancer patients. Thus, in order to enhance anti-tumor immune responses, selective depletion of Treg is highly desired. We found that treatment with zoledronic acid (ZA) resulted in a selective decrease in the frequency of Treg that was associated with a significant increase in proliferation of T cells and natural killer (NK) cells in peripheral blood of patients with metastatic cancer. In vitro, genome-wide transcriptomic analysis revealed alterations in calcium signaling pathways in Treg following treatment with ZA. Furthermore, co-localization of the nuclear factor of activated T cells (NFAT) and forkhead box P3 (FOXP3) was significantly reduced in Treg upon ZA-treatment. Consequently, reduced expression levels of CD25, STAT5 and TGFβ were observed. Functionally, ZA-treated Treg had reduced capacity to suppress T and NK cell proliferation and anti-tumor responses compared with untreated Treg in vitro. Treatment with ZA to selectively inhibit essential signaling pathways in Treg resulting in reduced capacity to suppress effector T and NK cell responses represents a novel approach to inhibit Treg activity in patients with 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.