ArticleFrontiers in immunology2018
Valproic Acid Combined with Zoledronate Enhance γδ T Cell-Mediated Cytotoxicity against Osteosarcoma Cells
Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Interleukin-17A-Producing Gamma Delta T Cells Accelerate Mineralization in Human Dental Pulp Stem Cells.Cell biology international · 2026Article
- Central memory-enriched Vγ9Vδ2 γδ T cells via TGF-β expansion demonstrate enhancedFrontiers in immunology · 2025Article
- γδT cells, a key subset of T cell for cancer immunotherapy.Frontiers in immunology · 2025Review
- Advancements in osteosarcoma management: integrating immune microenvironment insights with immunotherapeutic strategies.Frontiers in cell and developmental biology · 2024Review
- Metabolic reprogramming in osteosarcoma.Pediatric discovery · 2023Review
- Human γδ T cells induce CD8Cancer immunology, immunotherapy : CII · 2023Article
- Enhancement of T cell infiltrationBioactive materials · 2023Article
- Article
- The Immune Landscape of Osteosarcoma: Implications for Prognosis and Treatment Response.Cells · 2021Review
- Epigenetic modulation of immune synaptic-cytoskeletal networks potentiates γδ T cell-mediated cytotoxicity in lung cancer.Nature communications · 2021Article
- Novel application of single-cell next-generation sequencing for determination of intratumoral heterogeneity of canine osteosarcoma cell lines.Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc · 2021Article
- Cancer immunotherapy with γδ T cells: many paths ahead of us.Cellular & molecular immunology · 2020Review
- A Review of T-Cell Related Therapy for Osteosarcoma.International journal of molecular sciences · 2020Review
- The Dual Roles of Human γδ T Cells: Anti-Tumor or Tumor-Promoting.Frontiers in immunology · 2020Review
- Innate Immune Cells: A Potential and Promising Cell Population for Treating Osteosarcoma.Frontiers in immunology · 2019Review
- Histone Deacetylase Inhibitor Modulates NKG2D Receptor Expression and Memory Phenotype of Human Gamma/Delta T Cells Upon Interaction With Tumor Cells.Frontiers in immunology · 2019Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The long-term survival of osteosarcoma has remained unchanged in the last several decades. Immunotherapy is proved to be a promising therapeutic strategy against osteosarcoma, especially for those with metastasis. Our previous study explored the sensibilization of zoledronate (ZOL) in γδ T cell-mediated cytotoxicity against osteosarcoma, but we have not yet elucidated the specific mechanism. Besides, high concentration is required to achieve these effects, whereas plasma ZOL concentration declines rapidly in the circulation. Valproic acid (VPA), a histone deacetylase inhibitor commonly used as the antiepileptic drug, has attracted much attention due to its synergistic antitumor efficacy with chemotherapy or immunotherapy. Here, we demonstrated that VPA combined with ZOL revealed the synergistic effect in enhancing antitumor efficacy of γδ T cells against osteosarcoma cells. This enhancement was mainly TCR-mediated and largely dependent on granule exocytose pathway. Of note, our findings indicated that ZOL sensitized osteosarcoma cells to γδ T cells by increasing the accumulation of the mevalonate pathway intermediates, which could be facilitated by VPA. We also found that this combination had similar effects on primary osteosarcoma cells. All the results suggested that VPA combined with ZOL could reduce the dose required to achieve a significant antitumor effect of γδ T cells, promoting it to be a novel therapy against osteosarcoma.
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