Huang Xin, Wang Cunchuan, Wang Ningxia
Department of Breast Surgery, The First Affiliated Hospital, Jinan University, 613 West Huangpu Road, Guangzhou, 510630, Guangdong, People's Republic of China.
Cancer Cell Int. 2021 Feb 16;21(1):113. doi: 10.1186/s12935-021-01815-0.
Breast cancer ranks second of new cases and fifth of death in 2018 worldwide. Cis-platinum (CDDP) has been used as a chemotherapy to treat breast cancer for years. However, CDDP can adversely disrupt immune function of host. Thus, development of new protocol that can minimize side effect and meanwhile elevate clinical efficacy of CDDP will eventually benefit cancer patients. Since Vγ9Vδ2 T cells can up-regulate immune function of cancer patients, therefore, our hypothesis is that introduction of Vγ9Vδ2 T cells could potentiate CDDP efficacy against breast cancer.
We used breast cancer cell line MDA-MB-231 as model cell to test our hypothesis. The cancer cell viability in vitro in the context of different dose of CDDP was analyzed by flow cytometry. The cytoskeleton alteration was visualized by confocal microscopy, and the ultrastructure of cell membrane was observed by atomic force microscopy. The mitochondrial function of MDA-MB-231 cells was detected as well by flow cytometry.
Comparing to either Vγ9Vδ2 T cells or CDDP alone, Vγ9Vδ2 T cells plus CDDP could more strikingly induce MDA-MB-231 cell membrane ultrastructure disruption and cytoskeleton disorder, and more significantly enhance the inhibition of CDDP on proliferation of MDA-MB-231 cells. At the same time, Vγ9Vδ2 T cells strengthened CDDP-induced mitochondrial dysfunction of cancer cells.
This work revealed that Vγ9Vδ2 T cells could synergistically enhance the inhibition activity of CDDP against breast cancer cells. Meanwhile, this in vitro proof-of-concept study implied the clinical prospect of the combining application of Vγ9Vδ2 T cells and CDDP in breast cancer therapy.
2018年，乳腺癌的新发病例数位居全球第二，死亡病例数位居第五。顺铂（CDDP）多年来一直被用作治疗乳腺癌的化疗药物。然而，CDDP会对宿主的免疫功能产生不利影响。因此，开发一种能够将副作用降至最低，同时提高CDDP临床疗效的新方案最终将使癌症患者受益。由于Vγ9Vδ2 T细胞可以上调癌症患者的免疫功能，因此，我们的假设是引入Vγ9Vδ2 T细胞可以增强CDDP对乳腺癌的疗效。
我们使用乳腺癌细胞系MDA-MB-231作为模型细胞来验证我们的假设。通过流式细胞术分析不同剂量CDDP作用下体外癌细胞的活力。通过共聚焦显微镜观察细胞骨架的变化，通过原子力显微镜观察细胞膜的超微结构。同时，通过流式细胞术检测MDA-MB-231细胞的线粒体功能。
与单独使用Vγ9Vδ2 T细胞或CDDP相比，Vγ9Vδ2 T细胞与CDDP联合使用能更显著地诱导MDA-MB-231细胞膜超微结构破坏和细胞骨架紊乱，更显著地增强CDDP对MDA-MB-231细胞增殖的抑制作用。同时，Vγ9Vδ2 T细胞增强了CDDP诱导的癌细胞线粒体功能障碍。
本研究表明，Vγ9Vδ2 T细胞可协同增强CDDP对乳腺癌细胞的抑制活性。同时，这项体外概念验证研究暗示了Vγ9Vδ2 T细胞与CDDP联合应用于乳腺癌治疗的临床前景。
