論文 - 詳細
| RRC ID | 51643 |
|---|---|
| 著者 | Sugai S, Yoshikawa T, Iwama T, Tsuchiya N, Ueda N, Fujinami N, Shimomura M, Zhang R, Kaneko S, Uemura Y, Nakatsura T. |
| タイトル | Hepatocellular carcinoma cell sensitivity to Vγ9Vδ2 T lymphocyte-mediated killing is increased by zoledronate. |
| ジャーナル | Int J Oncol |
| Abstract |
The limited efficacy of vaccines in hepatocellular carcinoma (HCC), due to the low frequency of tumor-infiltrating cytotoxic T lymphocytes (CTLs), indicates the importance of innate immune surveillance, which assists acquired immunity by directly recognizing and eliminating HCC. Innate Vγ9Vδ2 T cells have major histocompatibility complex-unrestricted antitumor activity and are activated by phosphoantigens, which are upregulated in cancer cells by the nitrogen-containing bisphosphonate, zoledronate (Zol). A better understanding of HCC susceptibility to Zol and downstream γδ T cell-mediated killing is essential to optimize γδ T cell-mediated immunotherapy. This study systematically examined the interactions between γδ T cells and Zol-treated HCC cell lines (HepG2, HLE, HLF, HuH-1, JHH5, JHH7, and Li-7) in vitro. All HCC cell lines expressed the DNAX accessory molecule-1 ligands, poliovirus receptor, and Nectin-2, and γδ T cell-mediated killing of these cells was significantly enhanced by Zol. Small interfering RNA-mediated knockdown of these ligands did not affect the susceptibility to γδ T cell lysis. This killing activity was partly inhibited by mevastatin, an inhibitor of the mevalonate pathway, and markedly reduced by a monoclonal antibody to γ- and δ-chain T cell receptor, indicating that this is crucial for Zol-induced HCC killing. In addition, Zol-treated HCC cell lines triggered γδ T cell proliferation and induced production of Th1 and Th2, but not Th17, cytokines. The Zol concentration that enhanced HCC cell susceptibility to γδ T cell killing was lower than that required to directly inhibit HCC proliferation. Thus, γδ T cells may be important effector cells in the presence of Zol, especially where there are insufficient number of cancer antigen-specific CTLs to eliminate HCC. Our in vitro data support the proposal that Zol-treatment, combined with adaptive γδ T cell immunotherapy, may provide a feasible and effective approach for treatment of HCC. |
| 巻・号 | 48(5) |
| ページ | 1794-804 |
| 公開日 | 2016-5-1 |
| DOI | 10.3892/ijo.2016.3403 |
| PMID | 26936487 |
| PMC | PMC4809658 |
| MeSH | Antigens, Differentiation, T-Lymphocyte / metabolism* Carcinoma, Hepatocellular Cell Proliferation / drug effects Combined Modality Therapy Cytotoxicity, Immunologic Diphosphonates / pharmacology* Dose-Response Relationship, Drug Gene Expression Regulation, Neoplastic / drug effects Hep G2 Cells Humans Imidazoles / pharmacology* Immunity, Innate / drug effects Liver Neoplasms / immunology* Lymphocyte Activation / drug effects* T-Lymphocytes, Cytotoxic / immunology* Zoledronic Acid |
| IF | 3.899 |
| 引用数 | 7 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Li-7(RCB1941) Hep G2(RCB1648) T2(RCB1932) K562 |