2013/12/12 admin




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。


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。


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.