High-throughput sequencing of the T cell receptor in colorectal tumor infilt

项目总结/摘要 结直肠癌（CRC）是美国癌症死亡率的第二大原因。管理 包括需要准确确定患者预后和检测以下进展 疗法我们假设，肿瘤浸润淋巴细胞（TIL）计数和克隆性将能够更多地 比现有的基于使用疾病分期的方法更准确地预测患者结果 只.我们还假设，在治疗后测量来自血液的T细胞中的TIL克隆， 提供了一种准确预测CRC进展的方法。越来越多的证据支持我们的假设 上皮内肿瘤浸润淋巴细胞（TIL）的存在与患者的预后密切相关 在CRCs和许多其他疾病中。我们成功的机会是基于我们开发的新技术。 团队虽然目前用于评估TIL的技术不适合用于临床环境，但我们将使用 我们的团队开发的新技术，可以重复和定量地测量 和特定样品中TIL的克隆性。Immunoseq定量分析重排的T细胞受体 CDR 3链。我们将联合收割机这些措施与其他因素，以得出一个预测指标，可以 实际用于临床环境。为了得出我们的指标，我们将测量结肠癌活检切片， 在两个时间点（基线和6个月）从80例II期和III期结肠中采集匹配的血液样本 至少有两年临床随访的癌症患者。

PROJECT SUMMARY/ABSTRACT Colorectal cancers (CRC) are the second leading cause of cancer mortality in the United States. Management of CRC patients includes the need to accurately ascertain patient prognosis and to detect progression following therapy. We hypothesize that Tumor Infiltrating Lymphocyte (TIL) count and clonality will be able to more accurately predict patient outcome than currently existing approaches that are based on using disease stage only. We also hypothesize that measuring the TIL clones in T cells derived from blood following therapy will provide a method to accurately predict progression of CRC. Our hypothesis is supported by growing evidence that the presence of intraepithelial Tumor Infiltrating Lymphocytes (TILs) is strongly related to patient outcome in CRCs and many other diseases. Our opportunity to succeed is based on new technologies developed by our team. While current technologies for assessing TILs are not appropriate for use in a clinical setting, we will use new technologies developed by our team that can reproducibly and quantitatively measure the overall number and clonality of TILs in a specific sample. The assay Immunoseq quantifies rearranged T-cell receptor ¿ CDR3 chains. We will combine these measures with additional factors to derive a prognostic metric that can be practically used in a clinical setting. To derive our metric we will measure colon cancer biopsy sections and matched blood samples collected at two time points (baseline and 6 months) from 80 stage II and III colon cancer patients with at least two years of clinical follow-up.