Zysk Aneta, DeNichilo Mark O, Panagopoulos Vasilios, Zinonos Irene, Liapis Vasilios, Hay Shelley, Ingman Wendy, Ponomarev Vladimir, Atkins Gerald, Findlay David, Zannettino Andrew, Evdokiou Andreas
Discipline of Surgery, Breast Cancer Research Unit, Basil Hetzel Institute, University of Adelaide, Adelaide, South Australia, Australia.
Discipline of Surgery, Breast Biology Cancer Unit, Basil Hetzel Institute, University of Adelaide, Adelaide, South Australia, Australia.
Cancer Lett. 2017 Feb 1;386:141-150. doi: 10.1016/j.canlet.2016.11.013. Epub 2016 Nov 16.
Bone metastases occur in over 75% of patients with advanced breast cancer and are responsible for high levels of morbidity and mortality. In this study, ex vivo expanded cytotoxic Vγ9Vδ2 T cells isolated from human peripheral blood were tested for their anti-cancer efficacy in combination with zoledronic acid (ZOL), using a mouse model of osteolytic breast cancer. In vitro, expanded Vγ9Vδ2 T cells were cytotoxic against a panel of human breast cancer cell lines, and ZOL pre-treatment further sensitised breast cancer cells to killing by Vγ9Vδ2 T cells. Vγ9Vδ2 T cells adoptively transferred into NOD/SCID mice localised to osteolytic breast cancer lesions in the bone, and multiple infusions of Vγ9Vδ2 T cells reduced tumour growth in the bone. ZOL pre-treatment potentiated the anti-cancer efficacy of Vγ9Vδ2 T cells, with mice showing further reductions in tumour burden. Mice treated with the combination also had reduced tumour burden of secondary pulmonary metastases, and decreased bone degradation. Our data suggests that adoptive transfer of Vγ9Vδ2 T cell in combination with ZOL may prove an effective immunotherapeutic approach for the treatment of breast cancer bone metastases.
骨转移发生在超过75%的晚期乳腺癌患者中，是高发病率和死亡率的原因。在本研究中，使用溶骨性乳腺癌小鼠模型，测试了从人外周血中分离出的经体外扩增的细胞毒性Vγ9Vδ2 T细胞与唑来膦酸（ZOL）联合使用时的抗癌效果。在体外，扩增的Vγ9Vδ2 T细胞对一组人乳腺癌细胞系具有细胞毒性，ZOL预处理进一步使乳腺癌细胞对Vγ9Vδ2 T细胞的杀伤敏感。过继转移到NOD/SCID小鼠体内的Vγ9Vδ2 T细胞定位于骨中的溶骨性乳腺癌病变处，多次输注Vγ9Vδ2 T细胞可减少骨中的肿瘤生长。ZOL预处理增强了Vγ9Vδ2 T细胞的抗癌效果，小鼠的肿瘤负担进一步减轻。联合治疗的小鼠还减少了继发性肺转移的肿瘤负担，并减少了骨降解。我们的数据表明，Vγ9Vδ2 T细胞与ZOL过继转移可能是一种治疗乳腺癌骨转移的有效免疫治疗方法。
