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

结直肠肿瘤浸润中 T 细胞受体的高通量测序

• 批准号: 8702861
• 负责人: Harlan S. Robins
• 金额: $ 22.97万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-15 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8702861
• 关键词: Adjuvant Chemotherapy; Age; Biological Assay; Biopsy; Biopsy Specimen; Blood; Blood specimen; Cancer Etiology; Cancer Patient; Clinical; Clinical Management; Clonality; Colon Carcinoma; Colonic Neoplasms; Colorectal Cancer; Colorectal Neoplasms; Disease; Dose; Epithelial; Goals; Grant; High-Throughput Nucleotide Sequencing; Histology; Immune response; Immunohistochemistry; Localized Malignant Neoplasm; Lymphocyte Count; Measurement; Measures; Methods; Metric; Neoplasm Metastasis; Operative Surgical Procedures; Outcome; Patients; Prognostic Factor; Recurrence; Recurrent disease; Research; Risk; Sampling; Staging; Survival Rate; T cell response; T-Cell Receptor; T-Lymphocyte; TNM; Technology; Testing; Time; Tissues; Tumor-Infiltrating Lymphocytes; United States; Vital Status; base; disease classification; follow-up; improved; intraepithelial; member; molecular marker; mortality; new technology; outcome forecast; prognostic; repository; screening; sex; treatment planning; tumor; tumor progression; two-dimensional

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.

项目摘要/摘要 结直肠癌（CRC）是美国癌症死亡率的第二大原因。管理 CRC患者包括需要准确确定患者进展并检测进展 治疗。我们假设肿瘤浸润淋巴细胞（TIL）计数和克隆性将能够更多 准确地预测患者的结果，而不是目前基于使用疾病阶段的现有方法 仅有的。我们还假设测量在治疗后从血液中得出的T细胞中的TIL克隆将 提供一种准确预测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）的存在与患者结局密切相关 在CRC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。虽然当前用于评估TIL的技术不适合在临床环境中使用，但我们将使用 我们的团队开发的新技术可以重现和定量测量总数 和特定样本中的tils克隆性。该测定法量化了重新排列的T细胞受体„ CDR3链。我们将将这些措施与其他因素结合起来，以得出一个可以是预后的度量标准 实际上用于临床环境。为了得出我们的度量，我们将测量结肠癌活检切片和 从80阶段II和III颜色收集的两个时间点（基线和6个月）的匹配的血液样本 至少两年临床随访的癌症患者。