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

项目摘要/摘要 结直肠癌(CRC)是美国癌症死亡的第二大原因。管理 对结直肠癌患者的评估包括需要准确地确定患者的预后和检测病情进展 心理治疗。我们假设肿瘤浸润性淋巴细胞(TIL)计数和克隆性将能够更多地 比目前基于疾病分期的现有方法更准确地预测患者结果 只有这样。我们还假设，检测治疗后从血液中提取的T细胞中的TIL克隆将 提供了一种准确预测结直肠癌进展的方法。越来越多的证据支持我们的假设 上皮内肿瘤浸润性淋巴细胞(TIL)的存在与患者的预后密切相关 在癌症和许多其他疾病中。我们成功的机会是基于我们的 一队。虽然目前评估TIL的技术不适合在临床环境中使用，但我们将使用 我们团队开发的新技术，可以重复和定量地测量总数量 以及特定样本中TIL的克隆性。免疫电泳法测定重排T细胞受体� CDR3链。我们将把这些措施与其他因素结合起来，得出一个预测指标，该指标可以 在临床环境中实际使用。为了得出我们的指标，我们将测量结肠癌活检切片和 在两个时间点(基线和6个月)从80个II期和III期结肠采集匹配的血液样本 癌症患者至少有两年的临床随访。

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.