Digital genomic quantification of tumor-infiltrating lymphocytes.
Digital genomic quantification of tumor-infiltrating lymphocytes.
复制标题
DOI：
10.1126/scitranslmed.3007247
复制
发表时间：
2013-12-04
影响因子：
17.1
通讯作者：
Bielas JH
中科院分区：
文献类型：
--
作者：
Robins HS;Ericson NG;Guenthoer J;O'Briant KC;Tewari M;Drescher CW;Bielas JH
浸润性T淋巴细胞经常在恶性肿瘤中发现，并且提示宿主癌症免疫应答。多项独立研究已经证明，肿瘤浸润性T淋巴细胞（TIL）的存在和数量与生存率的增加密切相关。然而，由于方法学因素，TIL对预后的确切影响仍然是个谜，标准预后面板中包含的TIL一直是有限的。例如，一些报告列举了所有CD 3+细胞，一些报告仅计数细胞毒性CD 8 + T细胞，并且用于将肿瘤评分为TIL阳性或阴性的标准在研究中不一致。为了解决这一局限性，我们引入了一种强大的基于DNA的数字检测方法，称为QuanTILfy，以可靠且廉价地计数TIL并评估组织样本（包括肿瘤）中的T细胞克隆性。我们通过诊断T系急性淋巴细胞白血病（T-ALL）以及原发性和转移性卵巢癌中TIL的准确、灵敏和高度可重复测量来证明这种方法的克隆特异性。我们的实验证明了较高的TIL计数与卵巢癌患者生存率提高之间的相关性，并且与先前的观察结果一致，即针对卵巢癌的免疫应答是一个有意义的独立预后因素。令人惊讶的是，该研究中所有肿瘤的TIL库是多样的，没有显著的寡克隆扩增。此外，由于TIL的测量和表征的可变性限制了其作为生物标志物的临床实用性，因此这些结果突出了稳健的、可扩增的基于DNA的测定在评估各种癌症类型中的TIL中的显著转化潜力。
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 T-lymphocytes (TILs) are strongly correlated with increased survival. However, due to 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 negative are inconsistent among studies. To address this limitation, we introduce a robust digital DNA-based assay, termed QuanTILfy, to reliably and inexpensively 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-lineage acute lymphoblastic leukemia (T-ALL) 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 prior 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, as 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.
登录
查看更多内容
DOI：
10.1073/pnas.0509182102
发表时间：
2005-12-20
影响因子：
11.1
作者：
Sato, E;Olson, SH;Odunsi, K
通讯作者：
Odunsi, K
影响因子：
4.8
作者：
Chang, Qing;Hedley, David
通讯作者：
Hedley, David
影响因子：
45.3
作者：
Azimi, Farhad;Scolyer, Richard A.;Thompson, John F.
通讯作者：
Thompson, John F.
影响因子：
2.1
作者：
Valasek, MA;Repa, JJ
通讯作者：
Repa, JJ
DOI：
10.1007/s00262-013-1446-2
发表时间：
2013-09
期刊：
Cancer immunology, immunotherapy : CII
影响因子：
--
作者：
Sherwood AM;Emerson RO;Scherer D;Habermann N;Buck K;Staffa J;Desmarais C;Halama N;Jaeger D;Schirmacher P;Herpel E;Kloor M;Ulrich A;Schneider M;Ulrich CM;Robins H
通讯作者：
Robins H