Analysis of Immune Cells from Human Mammary Ductal Epithelial Organoids Reveals Vδ2+ T Cells That Efficiently Target Breast Carcinoma Cells in the Presence of Bisphosphonate.
Analysis of Immune Cells from Human Mammary Ductal Epithelial Organoids Reveals Vδ2+ T Cells That Efficiently Target Breast Carcinoma Cells in the Presence of Bisphosphonate.
复制标题
DOI：
10.1158/1940-6207.capr-15-0370-t
复制
发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Gumperz JE
中科院分区：
文献类型：
--
作者：
Zumwalde NA;Haag JD;Sharma D;Mirrielees JA;Wilke LG;Gould MN;Gumperz JE
制定加强癌症预防的策略是一个首要目标，特别是考虑到最近对导管原位癌等侵袭前状态的手术治疗的关注。促进白细胞扫描新生肿瘤转化的有效免疫监视是实现这一目标的潜在手段。由于大多数乳腺癌发生在导管上皮内，加强保护性免疫监视可能需要在正常情况下针对这些部位发现的一种或多种独特的淋巴细胞类型。在这里，我们描述了非癌性人乳腺组织上皮内淋巴细胞室的特征，并确定了一个T淋巴细胞亚群，可以通过药物靶向来增强它们对乳腺癌细胞的反应。具体来说，Vδ2+ γδ T细胞一直存在于乳腺导管上皮类器官的制备中，它们对唑来膦酸（一种氨基二膦酸盐药物）有增殖反应。来自乳腺导管类器官的Vδ2+ T细胞产生抗肿瘤细胞因子IFN-γ并有效杀死双磷酸盐脉冲乳腺癌细胞。这些发现表明，利用Vδ2+ γδ T细胞对fda批准的双膦酸盐药物的反应能力，作为一种新的免疫治疗方法，可以抑制乳腺癌的生长。
Developing strategies to enhance cancer prevention is a paramount goal, particularly given recent concerns about surgical treatment of pre-invasive states such as ductal carcinoma in situ. Promoting effective immunosurveillance by leukocytes that scan for nascent neoplastic transformations represents a potential means to achieve this goal. Since most breast cancers arise within the ductal epithelium, enhancing protective immunosurveillance will likely necessitate targeting one or more of the distinctive lymphocyte types found in these sites under normal conditions. Here, we have characterized the intraepithelial lymphocyte compartment of non-cancerous human breast tissue and identified a subset of T lymphocytes that can be pharmacologically targeted to enhance their responses to breast cancer cells. Specifically, Vδ2+ γδ T cells were consistently present in preparations of mammary ductal epithelial organoids and they proliferated in response to zoledronic acid, an aminobisphosphonate drug. Vδ2+ T cells from breast ductal organoids produced the anti-tumor cytokine IFN-γ and efficiently killed bisphosphonate-pulsed breast carcinoma cells. These findings demonstrate the potential for exploiting the ability of Vδ2+ γδ T cells to respond to FDA-approved bisphosphonate drugs as a novel immunotherapeutic approach to inhibit the outgrowth of breast cancers.