(PQC3) Using an Immunoscore to Assess Tumor-medicated Immune Variations in African -American

(PQC3) 使用免疫评分评估非裔美国人的肿瘤治疗免疫变异

基本信息

批准号：
8792043
负责人：
Timothy Wallace
金额：
$ 12.72万
依托单位：
BON SECOURS RICHMOND COMMUNITY HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-22 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8792043
关键词：
Address Affect African American Androgen Receptor Androgens Area Biochemical Biological Factors CD3 Antigens CD8-Positive T-Lymphocytes CD8B1 gene Cancer Patient Caucasians Caucasoid Race Cell Proliferation Cells Clinical Colorectal Cancer Data Disease Disease Progression Epithelial Ethnic group Event Formalin Future Gene Expression Generations Genes Gleason Grade for Prostate Cancer Goals Immune Immune response Individual Invaded Knowledge Lesion Lymphocyte Malignant Neoplasms Malignant neoplasm of prostate Mediating Metastatic Prostate Cancer Methodology Methods Neoplasm Metastasis Nodule Outcome Paraffin Embedding Patients Population Process Prostate Prostatectomy Prostatic Neoplasms Proteins Race Radical Prostatectomy Recurrence Regression Analysis Relative (related person)Reproducibility Research Risk Factors Sampling Signal Transduction Solid Neoplasm Specimen Staining method Stains Statistical Models T-Lymphocyte Testing Tissue Banking Tissue Banks Tissue Microarray Tissues Translating Tumor-Infiltrating Lymphocytes United States Variant Work base biobank cancer health disparity cohort comparative epithelial to mesenchymal transition follow-up health disparity high risk improved men mortality prognostic public health relevance racial difference receptor statistics treatment response tumor tumor microenvironment

项目摘要

DESCRIPTION (provided by applicant): Despite a body of evidence demonstrating the importance of the tumor-mediated immune response to the outcome of prostate cancer patients, no studies have adequately evaluated the tumor-mediated immune response in African American patients. Given that the African American race is a risk factor for more aggressive and lethal prostate cancer, the purpose of this study is to test the overall hypothesis that difference in the quantity and localization of tumor-infiltrating lymphocytes into the prostate gland correlat with PCa racial health disparities and that androgen signaling regulates this process. For this study, we will utilize a prostate tissue biorepository collected between 2003 and 2013, containing over 6,500 archival prostate cancer specimens, 25% (1,630) of which are from African American men. To test our hypothesis in a definitive way, we will utilize the concept of an "immunoscore." The immunoscore, a combined score based on the quantitation of CD3+ and CD8+ T lymphocytes in a tumor, has already been found to be a strong predictive indicator in patients with colorectal cancer and is only starting to be explored for other solid tumor types. In our Specific Aim 1, we will adapt existing immunoscoring methodology to be compatible with and applicable to prostate cancer, and will test the reproducibility and robustness of calculating the prostate cancer immunoscore in a small, preliminary panel of African American and Caucasian patients from our tissue bank. In our Specific Aim 2, we will determine the prostate cancer immunoscore and androgen receptor status in a large cohort of African American (1,630) and Caucasian (1,630) patients, for which we also have 10-year follow-up data. We will then be able to determine if differences exist between African Americans and Caucasians with respect to: prostate cancer immunoscores, the spectrum/quantity of tumor-infiltrating T lymphocytes (CD3+, CD4+, and CD8+), and/or androgen receptor status; and if race is predictive of any of these variables. In our Specific Aim 3, we will perform Cox regression analysis and statistical modeling to determine if the prostate cancer immunoscore and/or AR status are predictors of long-term clinical outcomes (biochemical recurrence and/or disease-specific mortality) in African American and/or Caucasian patients with localized prostate cancer. If so, we will be able to construct an immunoscore-based classifier that clinicians can use to better predict outcome in their African American patients with prostate cancer-something that currently doesn't exist and is desperately needed. This work will also provide the clinical justification for future mechanisti studies surrounding race, tumor-infiltrating T lymphocytes, and androgen signaling in prostate cancer.

描述（由申请人提供）：尽管大量证据表明肿瘤介导的免疫反应对前列腺癌患者的结果的重要性，但没有研究充分评估非裔美国患者中肿瘤介导的免疫反应。鉴于非裔美国人种族是更具侵袭性和致命性的前列腺癌的危险因素，本研究的目的是检验总体假设，即前列腺中肿瘤浸润淋巴细胞的数量和定位差异与 PCa 种族健康相关差异，并且雄激素信号调节这一过程。在本研究中，我们将利用 2003 年至 2013 年间收集的前列腺组织生物样本库，其中包含 6,500 多个档案前列腺癌样本，其中 25% (1,630) 来自非裔美国男性。为了以明确的方式检验我们的假设，我们将利用“免疫评分”的概念。免疫评分是基于肿瘤中 CD3+ 和 CD8+ T 淋巴细胞定量的综合评分，已被发现是结直肠癌患者的强有力的预测指标，并且刚刚开始探索其他实体瘤类型。在我们的具体目标 1，我们将调整现有的免疫评分方法，使其与前列腺癌兼容并适用，并将在我们组织库中的一小部分初步小组中测试计算前列腺癌免疫评分的再现性和稳健性。在我们的具体目标 2 中，我们将确定一大群非裔美国人 (1,630 名) 和白种人 (1,630 名) 患者的前列腺癌免疫评分和雄激素受体状态，我们也有 10 年的随访数据。然后，我们将能够确定非裔美国人和白种人之间在以下方面是否存在差异：前列腺癌免疫评分、肿瘤浸润 T 淋巴细胞（CD3+、CD4+ 和 CD8+）的谱/数量和/或雄激素受体状态；以及种族是否可以预测这些变量中的任何一个。在我们的具体目标 3 中，我们将进行 Cox 回归分析和统计建模，以确定前列腺癌免疫评分和/或 AR 状态是否是非裔美国人和非裔美国人中长期临床结果（生化复发和/或疾病特异性死亡率）的预测因子。 /或患有局限性前列腺癌的白种人患者。如果是这样，我们将能够构建一个基于免疫评分的分类器，临床医生可以用它来更好地预测非洲裔美国前列腺癌患者的结果——目前还不存在但迫切需要这种分类器。这项工作还将为未来围绕种族、肿瘤浸润 T 淋巴细胞和前列腺癌雄激素信号传导的机制研究提供临床依据。