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Science:新数码DNA可对任何存在于某组织样本中T细胞进行定量和定性

2013/12/12 华泰昕生物|HyperCyte 已读

摘要:
弗雷德哈钦森癌症研究中心的研究人员最新研发一种新的以数码方式计数T细胞的DNA检测可预测卵巢癌患者的存活率。相关文章发表于2013年12月04日的《Science》杂志上。
华泰昕

 

一种新的以数码方式计数T细胞的DNA检测可对卵巢癌患者的存活预测有帮助。这些发现增添了证据,这些证据提示含有大量的一种被称为肿瘤浸润淋巴细胞(TIL)的T细胞与卵巢癌患者存活率的改善有关。

Harlan Robins及其同事研发了一种基于DNA的测试,它能够以数码的方式对任何存在于某组织样本中的T细胞进行定量和定性。该技术是通过对每个T细胞上的独特的T细胞DNA序列或“条码”进行扫描以确定存在着多少以及什么样的T细胞而工作的。在对卵巢癌患者的T细胞进行扫描时他们发现,TIL计数的增加与存活率的改善相关,而转移性肿瘤要比原发性肿瘤呈现出更高的TIL计数。

研究人员惊异地发现,在卵巢肿瘤中有着明显的T细胞多样性(而不是T细胞的克隆性扩展),它表明对癌症的免疫反应是多方面的,而不是聚焦于一种或几个异常的肿瘤蛋白。数码T细胞计数可能对其它癌症也有用,因为研究人员显示,该方法可在一个血液样本中用于诊断T细胞性急性淋巴母细胞性白血病。

这些结果提示,该廉价且可靠的数码DNA检测可以是一种用于更为个性化的癌症诊断及治疗的强有力的工具。由Franck Pagès撰写的一则相关的《焦点》文章进一步讨论了此项研究的意义。

原文摘要:

Digital Genomic Quantification of Tumor-Infiltrating Lymphocytes

Harlan S. Robins, Nolan G. ericson, Jamie Guenthoer, Kathy C. O’Briant, Muneesh Tewari,Charles W. Drescher and Jason H. Bielas

Infiltrating T lymphocytes are frequently found in malignant tumors and are suggestive of a host cancer immune response. Multiple independent studies have documented that the presence and quantity of tumor-infiltrating lymphocytes (TILs) are strongly correlated with increased survival. However, because of methodological factors, the exact effect of TILs on prognosis has remained enigmatic, and inclusion of TILs in standard prognostic panels has been limited. For example, some reports enumerate all CD3+ cells, some count only cytotoxic CD8+T cells, and the criteria used to score tumors as TIL-positive or TIL-negative are inconsistent among studies. To address this limitation, we introduce a robust digital DNA-based assay, termed QuanTILfy, to count TILs and assess T cell clonality in tissue samples, including tumors. We demonstrate the clonal specificity of this approach by the diagnosis of T cell acute lymphoblastic leukemia and the accurate, sensitive, and highly reproducible measurement of TILs in primary and metastatic ovarian cancer. Our experiments demonstrate an association between higher TIL counts and improved survival among women with ovarian cancer, and are consistent with previous observations that the immune response against ovarian cancer is a meaningful and independent prognostic factor. Surprisingly, the TIL repertoire is diverse for all tumors in the study with no notable oligoclonal expansions. Furthermore, because variability in the measurement and characterization of TILs has limited their clinical utility as biomarkers, these results highlight the significant translational potential of a robust, standardizable DNA-based assay to assess TILs in a variety of cancer types.

 

原文链接:http://stm.sciencemag.org/content/5/214/214ra169