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Anti-tumor Immunity in Myeloma

骨髓瘤的抗肿瘤免疫

基本信息

批准号：
8625711
负责人：
MADHAV V DHODAPKAR
金额：
$ 31.39万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-03-08 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8625711
关键词：
Beds Biology Bone Marrow Cell physiology Cells Chronic Clinical Data Dendritic Cell Pathway Dendritic Cells Disease Progression Epithelial Equilibrium Exposure to Gene Expression Genetic Genome Stability Genomic Instability Growth Human Immune Immune response Immune system Immunity Inflammation Inflammatory Lead Link Malignant Neoplasms Mediating Memory Monoclonal gammopathy of uncertain significance Multiple Myeloma Myelogenous Myeloid Cells Patients Plasma Cell Neoplasm Play Preneoplastic Conditions Prevention Property Recruitment Activity Recurrent disease Regulation Role Signal Transduction T-Cell Activation T-Lymphocyte Testing Tumor Immunity Tumor-Derived Work activation-induced cytidine deaminase base cohort immune function in vivo inhibitor/antagonist neoplastic cell novel novel strategies public health relevance response success tumor tumor growth tumor microenvironment

项目摘要

DESCRIPTION (provided by applicant): Interactions between tumor cells and the microenvironment (TME) have a major impact on the biology of myeloma (MM) and its precursor monoclonal gammopathy of undetermined significance (MGUS). This application is a continuation of our prior work wherein we characterized several aspects of TME in MM. A theme from our prior work is that transition of MGUS to MM is associated with several changes in TME, with loss of anti-tumor immunity and progressive inflammation. Herein we will pursue the link between properties of tumor cells and changes in TME. Based on our preliminary studies, we posit that secretion of wnt inhibitors by tumor cells and the recruitment of myeloid cells play a major role in the altered balance of immunity and inflammation. In Aim 1, we will pursue the effect of wnt inhibitors on the regulation of host immune response. In Aim 2, we will further characterize the crosstalk between myeloid cells and myeloma in the regulation of genomic instability. These studies may provide several targets to restore the dysregulation of immunity versus inflammation and restrict genomic instability in this cancer.

描述（由申请人提供）：肿瘤细胞与微环境（TME）之间的相互作用对骨髓瘤（MM）及其意义不明的前体单克隆丙种球蛋白病（MGUS）的生物学具有重大影响。本申请是我们先前工作的延续，其中我们表征了MM中TME的几个方面。我们先前工作的主题是MGUS向MM的转变与TME的几个变化相关，具有抗肿瘤免疫力的丧失和进行性炎症。在此，我们将探讨肿瘤细胞的性质和TME变化之间的联系。基于我们的初步研究，我们认为肿瘤细胞分泌wnt抑制剂和骨髓细胞的募集在免疫和炎症平衡的改变中起主要作用。在目标1中，我们将追求wnt抑制剂对宿主免疫应答的调节的作用。在目标2中，我们将进一步表征骨髓细胞和骨髓瘤在基因组不稳定性调节中的串扰。这些研究可能提供几个目标，以恢复免疫与炎症的失调，并限制这种癌症的基因组不稳定性。