ArticleOncoimmunology
Stress-related and homeostatic cytokines regulate Vγ9Vδ2 T-cell surveillance of mevalonate metabolism.
Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 45 citations in OpenAlex.
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- CD96 marks a phenotypically distinct checkpoint-associated HCV-specific CD8+ T-cell subset featuring memory-associated states.Frontiers in immunology · 2026Article
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- Effects of functional antioxidants on the expansion of gamma delta T-cells and their cellular cytotoxicity against bladder cancer cells.BMC cancer · 2025Article
- CD56 on immune and tumor cells: what is known and beyond?Clinical and experimental immunology · 2025Review
- AI-assisted peripheral immune profiling reveals unconventional lymphocyte signatures associated with prognosis in soft tissue sarcoma patients.Frontiers in immunology · 2025Article
- γδT cells, a key subset of T cell for cancer immunotherapy.Frontiers in immunology · 2025Review
- An organotypic human melanoma-in-skin model as anImmuno-oncology technology · 2024Article
- Immune profiling of age and adjuvant-specific activation of human blood mononuclear cells in vitro.Communications biology · 2024Article
- CTLs heterogeneity and plasticity: implications for cancer immunotherapy.Molecular cancer · 2024Review
- Natural Killer T-like Cells: Immunobiology and Role in Disease.International journal of molecular sciences · 2023Review
- The role of natural killer T cells in liver transplantation.Frontiers in cell and developmental biology · 2023Review
- Single-cell Characterization of the Cellular Landscape of Acral Melanoma Identifies Novel Targets for Immunotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Potentiating Vγ9Vδ2 T cell proliferation and assessing their cytotoxicity towards adherent cancer cells at the single cell level.Biology open · 2022Article
- Gamma Delta T-Cell Based Cancer Immunotherapy: Past-Present-Future.Frontiers in immunology · 2022Review
- Review
- Dichotomous and stable gamma delta T-cell number and function in healthy individuals.Journal for immunotherapy of cancer · 2021Article
- Cancer immunotherapy with γδ T cells: many paths ahead of us.Cellular & molecular immunology · 2020Review
- Review
- Gamma/Delta T Cells in the Course of Healthy Human Pregnancy: Cytotoxic Potential and the Tendency of CD8 Expression Make CD56+ γδT Cells a Unique Lymphocyte Subset.Frontiers in immunology · 2020Article
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Authors and funding
6 authors at 3 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The potentially oncogenic mevalonate pathway provides building blocks for protein prenylation and induces cell proliferation and as such is an important therapeutic target. Among mevalonate metabolites, only isopentenyl pyrophosphate (IPP) has been considered to be an immunologically relevant antigen for primate-specific, innate-like Vγ9Vδ2 T cells with antitumor potential. We show here that Vγ9Vδ2 T cells pretreated with the stress-related, inflammasome-dependent cytokine interleukin 18 (IL-18) were potently activated not only by IPP but also by all downstream isoprenoid pyrophosphates that exhibit combined features of antigens and cell-extrinsic metabolic cues. Vγ9Vδ2 T cells induced this way effectively proliferated even under severe lymphopenic conditions and the antioxidant N-acetylcysteine significantly improved reconstitution of γδ T cells predominantly with a central memory phenotype. The homeostatic cytokine IL-15 induced the differentiation of effector cells in an antigen-independent fashion, which rapidly produced abundant interferon γ (IFNγ) upon antigen re-encounter. IL-15 induced effector γδ T cells displayed increased levels of the cytotoxic lymphocyte-associated proteins CD56, CD96, CD161 and perforin. In response to stimulation with isoprenoid pyrophosphates, these effector cells upregulated surface expression of CD107a and exhibited strong cytotoxicity against tumor cells in vitro. Our data clarify understanding of innate immunosurveillance mechanisms and will facilitate the controlled generation of robust Vγ9Vδ2 T cell subsets for effective cancer immunotherapy.
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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.