ArticleThe Journal of clinical investigation2020
γ9δ2T cell diversity and the receptor interface with tumor cells.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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The trial behind it
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Who cites it
45 citing papers in PubMed, 71 citations in OpenAlex.
- Adoptive transfer of zoledronate-expanded autologous Vγ9Vδ2 T-cells in patients with treatment-refractory non-small-cell lung cancer: a multicenter, open-label, single-arm, phase 2 study.Journal for immunotherapy of cancer · 2020Trial
- Phase II Trial of Maintenance Treatment With IL2 and Zoledronate in Multiple Myeloma After Bone Marrow Transplantation: Biological and Clinical Results.Frontiers in immunology · 2020Trial
- γδ T cells at the interface of innate and adaptive immunity in cancer.Journal for immunotherapy of cancer · 2026Review
- Harnessing Vδ1Frontiers in immunology · 2026Review
- Cis- and trans-binding chimeric costimulatory receptors enhance T-cell fitness and tumor control.Cellular & molecular immunology · 2026Article
- Peptide hydrogel boosts the cytotoxic and metabolic fitness of Vγ9Vδ2 T cells in melanoma immunotherapy.Frontiers in immunology · 2026Article
- Pre-existing activation states shape functional heterogeneity of human Vγ9Vδ2 T cells.Frontiers in immunology · 2026Article
- Cis- and trans-binding chimeric costimulatory receptors enhance T-cell fitness and tumor control.Cellular & molecular immunology · 2026Article
- Autologous profiling reveals inter-patient heterogeneity in Vδ2Journal for immunotherapy of cancer · 2025Article
- Article
- Disrupting the balance between activating and inhibitory receptors of γδT cells for effective cancer immunotherapy.Nature reviews. Cancer · 2025Review
- Mechanisms and Functions of γδ T Cells in Tumor Cell Recognition.Current oncology (Toronto, Ont.) · 2025Review
- A Brief Molecular History of Vγ9Vδ2 TCR-Mediated Phosphoantigen Sensing.Immunological reviews · 2025Review
- Unusual Partners: γδ-TCR-Based T Cell Therapy in Combination with Oncolytic Virus Treatment for Diffuse Midline Gliomas.International journal of molecular sciences · 2025Article
- Characterization of the Bone Marrow Lymphoid Microenvironment and Discovery of Prognostic Immune-Related Factors in Acute Myeloid Leukemia.International journal of molecular sciences · 2024Article
- A nonadjuvanted HLA-restricted peptide vaccine induced both T and B cell immunity against SARS-CoV-2 spike protein.Scientific reports · 2024Article
- Vγ9Vδ2 T cells recognize butyrophilin 2A1 and 3A1 heteromers.Nature immunology · 2024Article
- Unsynchronized butyrophilin molecules dictate cancer cell evasion of Vγ9Vδ2 T-cell killing.Cellular & molecular immunology · 2024Article
- Article
- Dual targeting of cancer metabolome and stress antigens affects transcriptomic heterogeneity and efficacy of engineered T cells.Nature immunology · 2024Article
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 3 countries.
Funding
Abstract
γ9δ2T cells play a major role in cancer immune surveillance, yet the clinical translation of their in vitro promise remains challenging. To address limitations of previous clinical attempts using expanded γ9δ2T cells, we explored the clonal diversity of γ9δ2T cell repertoires and characterized their target. We demonstrated that only a fraction of expanded γ9δ2T cells was active against cancer cells and that activity of the parental clone, or functional avidity of selected γ9δ2 T cell receptors (γ9δ2TCRs), was not associated with clonal frequency. Furthermore, we analyzed the target-receptor interface and provided a 2-receptor, 3-ligand model. We found that activation was initiated by binding of the γ9δ2TCR to BTN2A1 through the regions between CDR2 and CDR3 of the TCR γ chain and modulated by the affinity of the CDR3 region of the TCRδ chain, which was phosphoantigen independent (pAg independent) and did not depend on CD277. CD277 was secondary, serving as a mandatory coactivating ligand. We found that binding of CD277 to its putative ligand did not depend on the presence of γ9δ2TCR, did depend on usage of the intracellular CD277, created pAg-dependent proximity to BTN2A1, enhanced cell-cell conjugate formation, and stabilized the immunological synapse (IS). This process critically depended on the affinity of the γ9δ2TCR and required membrane flexibility of the γ9δ2TCR and CD277, facilitating their polarization and high-density recruitment during IS formation.
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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.