Leukocyte Biomarkers for Predicting Human Breast Cancer Outcomes

描述（由申请人提供）：现在已经确定，白细胞长期浸润到肿瘤组织中会增强实体瘤的发展。许多实验和临床研究表明，促进肿瘤的白细胞基本上调节了癌症发展的各个方面。然而，与发展中的乳腺癌（bc）相关的单个白细胞亚型的分子特性尚不充分了解。我们的首要假设是，人类BC中的白细胞生物标志物可以提供有关BC结果的预后和预测信息，并且这些也可以用作设计新的个性化诊断和治疗药物的平台。这项TMEN提案是基于我们的共同目标，即与BC相比，对正常乳腺组织中白细胞的组成和转录组特征有一个全面的了解。基于与BC分期、结果或治疗反应相关的预测性免疫生物标志物的鉴定，我们将产生创新的、临床适用的诊断和可能的治疗，或用于非侵入性体内分子图像分析的联合“诊断”“探针”。这些新颖独特的试剂的开发将促进我们对BC肿瘤微环境的理解。因此，我们预测，BC中的免疫微环境不仅可以用来预测疾病复发的风险和对治疗的反应，还可以用来监测对治疗的反应，这些进展将改善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志物。项目2将揭示人类乳腺癌预后与白细胞转录组和新型白细胞生物标志物的相关性；项目3将推动白细胞生物标志物转化为临床应用的诊断和治疗探针。

DESCRIPTION (provided by applicant): 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.