Zoledronic acid-induced expansion of γδ T cells from early-stage breast cancer patients: effect of IL-18 on helper NK cells.

Zoledronic acid-induced expansion of γδ T cells from early-stage breast cancer patients: effect of IL-18 on helper NK cells.
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DOI:
10.1007/s00262-012-1368-4
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发表时间:
2013-04
影响因子:
5.8
通讯作者:
Tanaka, Yoshimasa
Tanaka, Yoshimasa
中科院分区:
医学3区
文献类型:
--
作者:
Sugie, Tomoharu;Murata-Hirai, Kaoru;Iwasaki, Masashi;Morita, Craig T.;Li, Wen;Okamura, Haruki;Minato, Nagahiro;Toi, Masakazu;Tanaka, Yoshimasa

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人γδ T细胞对唑来膦酸(Zol)预处理的多种肿瘤细胞显示出强大的细胞毒性。Zol在早期乳腺癌患者的辅助内分泌治疗或多发性骨髓瘤患者的标准化疗中显示出益处。虽然γδ T细胞可能参与了这种叠加效应,但早期乳腺癌患者的γδ T细胞的反应性尚未得到充分研究。在这项研究中,我们测定了早期和晚期乳腺癌患者的Vγ2Vδ2 T细胞的数量、频率和反应性,并研究了IL-18对其体外扩增的影响。低频率v - γ - 2v - δ2 T细胞患者的反应性明显降低。然而,IL-18增强了Vγ2Vδ2 T细胞和辅助NK细胞的体外增殖反应,无论是低频率还是高频率的Vγ2Vδ2 T细胞。单用Zol治疗乳腺癌患者可减少v - γ - 2v - δ2 T细胞数量,降低其体外反应性。这些结果表明,Zol可以引起早期乳腺癌患者γδ T细胞的免疫应答,但频繁的体内治疗会降低v - γ 2v δ2 T细胞的数量及其对刺激的反应性。
Human γδ T cells display potent cytotoxicity against various tumor cells pretreated with zoledronic acid (Zol). Zol has shown benefits when added to adjuvant endocrine therapy for patients with early-stage breast cancer or to standard chemotherapy for patients with multiple myeloma. Although γδ T cells may contribute to this additive effect, the responsiveness of γδ T cells from early-stage breast cancer patients has not been fully investigated. In this study, we determined the number, frequency, and responsiveness of Vγ2Vδ2 T cells from early- and late-stage breast cancer patients and examined the effect of IL-18 on their ex vivo expansion. The responsiveness of Vγ2Vδ2 T cells from patients with low frequencies of Vγ2Vδ2 T cells was significantly diminished. IL-18, however, enhanced ex vivo proliferative responses of Vγ2Vδ2 T cells and helper NK cells from patients with either low or high frequencies of Vγ2Vδ2 T cells. Treatment of breast cancer patients with Zol alone decreased the number of Vγ2Vδ2 T cells and reduced their ex vivo responsiveness. These results demonstrate that Zol can elicit immunological responses by γδ T cells from early-stage breast cancer patients but that frequent in vivo treatment reduces Vγ2Vδ2 T cell numbers and their responsiveness to stimulation.
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