Leukocyte Biomarkers for Predicting Human Breast Cancer Outcomes

现在公认的是，肿瘤组织中白细胞的慢性渗透促进了实体瘤的发展。许多实验和临床研究表明，促进肿瘤的白细胞基本上调控癌症发展的方方面面。然而，与发展中的乳腺癌(BCS)相关的单个白细胞亚型的分子性质还没有被充分了解。我们最重要的是 假设人类BC中的白细胞生物标志物可以提供预后和预测性 关于BC结果的信息，这些信息也可以被用作设计新的个性化诊断和治疗试剂的平台。这项TMEN建议是基于我们的集体目标，即与BC相比，全面了解正常乳腺组织中白细胞的组成和转录组特征。基于识别与BC分期、结果或治疗反应相关的基于免疫的预测性生物标记物，我们将产生创新的、临床适用的诊断和可能的治疗性，或用于非侵入性体内分子图像分析的组合式“诊断”“探针”。这些新颖独特的试剂的开发将促进我们对卑诗省肿瘤微环境的了解。因此，我们预测BC的免疫微环境不仅可以用来预测疾病复发的风险和治疗反应，而且还可以监测治疗反应，这些进展将共同改善BC患者的预后。因此，项目1将确定乳腺癌中具有临床意义的白细胞生物标记物。项目2将揭示人类乳腺癌的预后与白细胞转录本和新的白细胞生物标记物的相关性；项目3将推动白细胞生物标记物转化为临床适用的诊断和治疗探针

It is now well established that chronic infiltration of leukocytes into neoplastic tissue potentiates solid tumor development. Many experimental and clinical studies have revealed that tumor-promoting leukocytes regulate essentially all aspects of cancer development. However, the molecular natures of individual leukocyte subtypes associated with developing breast cancers (BCs) are inadequately understood. Our overarching hypothesis is that leukocyte biomarkers in human BC can provide prognostic and predictive information regarding BC outcomes, and that these can also be utilized as platforms for design of new, individualized diagnostic and therapeutic agents. This TMEN proposal is based on our collective goal of generating a comprehensive understanding of the composition and transcriptome characteristics of leukocytes in normal breast tissue as compared to BC. Based on identification of predictive immune-based biomarkers that correlate with BC stage, outcome or response to therapy, we will generate innovative, clinically applicable diagnostic and possibly therapeutic, or combined "theragnostic" "probes" for non-invasive in vivo molecular image analysis. Development of these novel and unique reagents will advance our understanding of the tumor microenvironment in BC. As such, we predict that the immune microenvironment In BC can be utilized and exploited to not only predict risk of recurrent disease, and response to therapy, but also to monitor response to therapy and together, these advances will improve outcomes for patients with BC. As such Project 1 will Identify clinically significant leukocyte biomarkers in breast cancer. Project 2 will reveal correlation of outcomes in human breast cancer with leukocyte transcriptomes and novel leukocyte biomarkers; and Project 3 will drive translation of leukocyte biomarkers into clinically applicable diagnostic and therapeutic probes