(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

• 批准号: 8930939
• 负责人: Timothy Wallace
• 金额: $ 15.27万
• 依托单位: BON SECOURS RICHMOND COMMUNITY HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-22 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8930939
• 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; 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; Health; 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; clinical predictors; cohort; comparative; epithelial to mesenchymal transition; follow-up; health disparity; high risk; improved; men; mortality; prognostic; racial difference; receptor; statistics; treatment response; tumor; tumor microenvironment

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）：尽管有大量证据表明肿瘤介导的免疫反应对前列腺癌患者预后的重要性，但没有研究对非裔美国人患者的肿瘤介导的免疫反应进行了充分评估。鉴于非裔美国人种族是更具侵略性和致命的前列腺癌的危险因素，这项研究的目的是检验总体假设，即肿瘤浸润淋巴细胞的数量和定位差异与前列腺腺体与PCA种族健康差异的相关性和雄激素信号调节这一过程。 在这项研究中，我们将利用2003年至2013年之间收集的前列腺组织生物座状，其中包含6,500多个档案前列腺癌标本，其中25％（1,630）来自非裔美国人。为了以明确的方式检验我们的假设，我们将利用“免疫科”的概念。免疫科目是基于肿瘤中CD3+和CD8+ T淋巴细胞定量的合并评分，已经发现是结直肠癌患者的强烈预测指标，并且刚刚开始探索其他实体瘤类型。在 我们的特定目的1，我们将适应现有的免疫科学方法与前列腺癌兼容并适用于前列腺癌，并将测试在非裔美国人和来自我们组织库中的非裔美国人的小型初步小组中计算前列腺癌免疫科的可重复性和鲁棒性。在我们的特定目标2中，我们将确定大量非裔美国人（1,630）和高加索人（1,630）患者的前列腺癌免疫和雄激素受体状态，为此我们还拥有10年的随访数据。然后，我们将能够确定非洲裔美国人和高加索人之间在以下方面的差异：前列腺癌免疫，肿瘤浸润T淋巴细胞（CD3+，CD4+和CD8+）的光谱/数量以及/或/OR雄激素受体状态；如果种族可以预测这些变量中的任何一个。在我们的特定目标3中，我们将执行COX回归分析和统计模型，以确定前列腺癌免疫和/或AR状态是否是非洲裔美国人的长期临床结局（生化复发和/或疾病特异性死亡率）的预测指标，以及/或患有局部前列腺癌的青年患者。如果是这样，我们将能够构建一个基于免疫科的分类器，临床医生可以用来更好地预测其前列腺癌症患者目前不存在并且迫切需要的非裔美国人患者的结果。这项工作还将为围绕种族，肿瘤渗透T淋巴细胞和前列腺癌中的雄激素信号的未来机械学研究提供临床理由。