ArticleOncoimmunology
Zoledronate can induce colorectal cancer microenvironment expressing BTN3A1 to stimulate effector γδ T cells with antitumor activity.
Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 51 citations in OpenAlex.
- γδ T cells in colorectal and liver cancer.Nature reviews. Gastroenterology & hepatology · 2026Review
- Anti-tumor efficacy and Vδ2 T-cell activation via EGFR antibody-drug conjugates featuring novel aminobisphosphonates.Scientific reports · 2025Article
- A regulatory variant rs9379874 in T1D risk region 6p22.2 affects BTN3A1 expression regulating T cell function.Acta diabetologica · 2025Article
- γδT cells, a key subset of T cell for cancer immunotherapy.Frontiers in immunology · 2025Review
- Progress of research on γδ T cells in colorectal cancer (Review).Oncology reports · 2024Review
- BTN3A1 expressed in cervical cancer cells promotes Vγ9Vδ2 T cells exhaustion through upregulating transcription factors NR4A2/3 downstream of TCR signaling.Cell communication and signaling : CCS · 2024Article
- Article
- Controversial role of γδ T cells in colorectal cancer.American journal of cancer research · 2024Review
- A Ménage à trois: NLRC5, immunity, and metabolism.Frontiers in immunology · 2024Review
- Article
- Comprehensively analysis of immunophenotyping signature in triple-negative breast cancer patients based on machine learning.Frontiers in pharmacology · 2023Article
- Targeting of colorectal cancer organoids with zoledronic acid conjugated to the anti-EGFR antibody cetuximab.Journal for immunotherapy of cancer · 2022Article
- BTN3A: A Promising Immune Checkpoint for Cancer Prognosis and Treatment.International journal of molecular sciences · 2022Review
- Up-regulation of BTN3A1 on CD14Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Preclinical platforms to study therapeutic efficacy of human γδ T cells.Clinical and translational medicine · 2022Article
- Potentiating Vγ9Vδ2 T cell proliferation and assessing their cytotoxicity towards adherent cancer cells at the single cell level.Biology open · 2022Article
- The Diverse Roles of γδ T Cells in Cancer: From Rapid Immunity to Aggressive Lymphoma.Cancers · 2021Review
- mGWAS identification of six novel single nucleotide polymorphism loci with strong correlation to gastric cancer.Cancer & metabolism · 2021Article
- B7-H3 confers resistance to Vγ9Vδ2 T cell-mediated cytotoxicity in human colon cancer cells via the STAT3/ULBP2 axis.Cancer immunology, immunotherapy : CII · 2021Article
- NLRC5 promotes transcription ofiScience · 2021Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amino-bis-phosphonates (N-BPs) such as zoledronate (Zol) have been used in anticancer clinical trials due to their ability to upregulate pyrophosphate accumulation promoting antitumor Vγ9Vδ2 T cells. The butyrophilin 3A (BTN3A, CD277) family, mainly the BTN3A1 isoform, has emerged as an important structure contributing to Vγ9Vδ2 T cells stimulation. It has been demonstrated that the B30.2 domain of BTN3A1 can bind phosphoantigens (PAg) and drive the activation of Vγ9Vδ2 T cells through conformational changes of the extracellular domains. Moreover, BTN3A1 binding to the cytoskeleton, and its consequent membrane stabilization, is crucial to stimulate the PAg-induced tumor cell reactivity by human Vγ9Vδ2 T cells. Aim of this study was to investigate the relevance of BTN3A1 in N-BPs-induced antitumor response in colorectal cancer (CRC) and the cell types involved in the tumor microenvironment. In this paper, we show that (i) CRC, exposed to Zol, stimulates the expansion of Vδ2 T lymphocytes with effector memory phenotype and antitumor cytotoxic activity, besides sensitizing cancer cells to γδ T cell-mediated cytotoxicity; (ii) this effect is partially related to BTN3A1 expression and in particular with its cellular re-distribution in the membrane and cytoskeleton-associated fraction; (iii) BTN3A1 is detected in CRC at the tumor site, both on epithelial cells and on tumor-associated fibroblasts (TAF), close to areas infiltrated by Vδ2 T lymphocytes; (iv) Zol is effective in stimulating antitumor effector Vδ2 T cells from
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