ArticleJournal for immunotherapy of cancer2021
Costimulation of γδTCR and TLR7/8 promotes Vδ2 T-cell antitumor activity by modulating mTOR pathway and APC function.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 32 citations in OpenAlex.
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- Current Strategies and Emerging Paradigms of Immunotherapy in Microsatellite Stable Colorectal Cancer: A Review Article.Clinical drug investigation · 2026Review
- The Role of Nuclear Factor Erythroid 2-Related Factor 2 in the Crosstalk Between Oxidative Stress and M1/M2 Microglial Polarization Following Ischemic Stroke.Molecular neurobiology · 2026Review
- The Immunological Landscape of the Tumor Microenvironment: Implications for Immunotherapy of Unresectable and Metastatic Soft Tissue Sarcomas.Current treatment options in oncology · 2026Review
- Soluble Sema4D From γδ T Cells Exerts Osteoblast Inhibition via Plexin-B/mTOR Signalling Contributing to Pathogenesis of Bisphosphonate-Related Osteonecrosis of the Jaws.Cell proliferation · 2026Article
- γδ T cells at the interface of innate and adaptive immunity in cancer.Journal for immunotherapy of cancer · 2026Review
- DR5 CAR-T cells target melanoma and suppress MDSCs with minimal toxicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Macrophage polarization in hematologic cancers: mechanisms and therapeutic strategies.Blood research · 2026Review
- CD47 signaling in aging and age-related diseases: mechanisms, challenges, and therapeutic opportunities.Biogerontology · 2025Review
- Expansion strategies for Vδ2 γδT cells in cancer immunotherapy: Activation, cytokines, and culture conditions.World journal of clinical oncology · 2025Review
- Comparison of clinical features by primary site in patients with biliary tract cancer who received gemcitabine-based chemotherapy: an exploratory analysis of JCOG1113.International journal of clinical oncology · 2025Article
- Development of Prognostic Features and Investigation of Therapeutic Insights Related to Non-Apoptotic Regulatory Cell Death in Colorectal Cancer.Applied biochemistry and biotechnology · 2025Article
- T Cell Development and Responses in Human Immune System Mice.Annual review of immunology · 2025Review
- Reduced T-Cell stemness underlies Th17 expansion and graft dysfunction in kidney transplant recipients.Frontiers in genetics · 2025Article
- The immunostimulatory activity ofFrontiers in pharmacology · 2025Article
- High-sensitive sensory neurons exacerbate rosacea-like dermatitis in mice by activating γδ T cells directly.Nature communications · 2024Article
- Constructing co-stimulation to boost TCR therapy.Nature cancer · 2024Article
- The cytotoxicity ofOncogene · 2023Article
- An HPK1 inhibitor enhanced the tumour response to anti-PD-1 immunotherapy in non-Hodgkin's lymphoma.Clinical and experimental medicine · 2023Article
- STAT proteins in cancer: orchestration of metabolism.Nature reviews. Cancer · 2023Review
Corrections and comments
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Authors and funding
24 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundGamma delta (γδ) T cells are attractive effector cells for cancer immunotherapy. Vδ2 T cells expanded by zoledronic acid (ZOL) are the most commonly used γδ T cells for adoptive cell therapy. However, adoptive transfer of the expanded Vδ2 T cells has limited clinical efficacy.
methodsWe developed a costimulation method for expansion of Vδ2 T cells in PBMCs by activating γδ T-cell receptor (γδTCR) and Toll-like receptor (TLR) 7/8 using isopentenyl pyrophosphate (IPP) and resiquimod, respectively, and tested the functional markers and antitumoral effects in vitro two-dimensional two-dimensional and three-dimensional spheroid models and in vivo models. Single-cell sequencing dataset analysis and reverse-phase protein array were employed for mechanistic studies.
resultsWe find that Vδ2 T cells expanded by IPP plus resiquimod showed significantly increased cytotoxicity to tumor cells with lower programmed cell death protein 1 (PD-1) expression than Vδ2 T cells expanded by IPP or ZOL. Mechanistically, the costimulation enhanced the activation of the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB/Akt)-the mammalian target of rapamycin (mTOR) pathway and the TLR7/8-MyD88 pathway. Resiquimod stimulated Vδ2 T-cell expansion in both antigen presenting cell dependent and independent manners. In addition, resiquimod decreased the number of adherent inhibitory antigen-presenting cells (APCs) and suppressed the inhibitory function of APCs by decreasing PD-L1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression in these cells during in vitro Vδ2 T-cell expansion. Finally, we showed that human Vδ2 T cells can be expanded from PBMCs and spleen of humanized NSG mice using IPP plus resiquimod or ZOL, demonstrating that humanized mice are a promising preclinical model for studying human γδ T-cell development and function.
conclusionsVδ2 T cells expanded by IPP and resiquimod demonstrate improved anti-tumor function and have the potential to increase the efficacy of γδ T cell-based therapies.
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