Anti-Tumor immunity in myeloma

骨髓瘤的抗肿瘤免疫

• 批准号: 7191728
• 负责人: MADHAV V DHODAPKAR
• 金额: $ 32.85万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-08 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7191728
• 关键词: Adjuvant; Animals; Antibodies; Antigen Targeting; Antigen-Presenting Cells; Antigens; Autologous Tumor Cell; B-Cell Neoplasm; Beds; Behavior; Blood; Bone Marrow Neoplasms; CD4 Positive T Lymphocytes; CD8B1 gene; Cancer Biology; Cell Communication; Cell physiology; Cells; Clinical; Clonal Expansion; Cross Presentation; Cytogenetics; Data; Dendritic Cells; Disease; Effector Cell; Environment; Enzymes; Exhibits; Frequencies; Generations; Genomics; Goals; Growth; Human; Immune; Immune response; Immune system; Immunity; In Situ; In Vitro; Lead; Learning; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of testis; Marrow; Modeling; Monoclonal Antibodies; Monoclonal gammopathy of uncertain significance; Multiple Myeloma; Myelogenous; Nature; Neoplasms; Outcome; Patients; Peptides; Phenotype; Physiologic pulse; Plasma Cells; Plasmablast; Play; Population; Population Heterogeneity; Premalignant; Primary Neoplasm; Proteins; Pulse taking; Resources; Risk; Role; Surface; T memory cell; T-Lymphocyte; Testing; Tumor Antigens; Tumor Burden; Tumor Immunity; Viral Tumor Antigens; cell transformation; gammopathy; in vivo; killer T cell; macrophage; neoplastic cell; neuronal cell body; novel; novel strategies; prevent; prognostic; response; tumor; uptake

DESCRIPTION (provided by applicant): Multiple myeloma is an incurable B cell tumor with limited treatment options. Our goal is to study the ability of the host immune system to resist this tumor in patients. Clonal expansion of transformed plasma cells with nearly all of the known genomic and cytogenetic changes found in myeloma can remain clinically stable for prolonged periods in patients with preneoplastic gammopathy (MGUS). Our preliminary studies suggest that these patients mount a vigorous and specific immune response against tumor cells in the tumor bed, which is not found in myeloma patients. Our hypothesis is that the host immune response plays a key role in controlling the malignant growth of tumor cells in patients, and this response is critically dependent on the context of tumor-dendritic celI-T cell interactions in vivo. MGUS-myeloma is a particularly useful model to study tumor-immune interactions, as it is possible in this tumor to isolate tumor and immune effector and antigen presenting cells directly from the bone marrow tumor bed, without the need for ex vivo culture and enzymatic treatments. Our long-term goal is to learn to harness the host immune response in an attempt to prevent progression of MGUS to myeloma. Our specific aims are 1) to study the nature of host anti-tumor CD4+ and CD8+ T cell response in the blood and tumor bed of patients with myeloma and MGUS; 2) to characterize the nature of antigen-presenting cells in the tumor bed and their interactions with tumor cells in situ; and 3) to study whether specific subpopulations of tumor cells can be specifically targeted to dendritic cells, the body's natural adjuvant. These studies should provide novel information about the interactions between tumor cells and immune system in the context of tumor microenvironment; and suggest novel strategies to boost anti-tumor immunity in patients targeting dendritic cells.

描述(申请人提供)：多发性骨髓瘤是一种无法治愈的B细胞肿瘤，治疗选择有限。我们的目标是研究宿主免疫系统抵抗患者这种肿瘤的能力。在骨髓瘤中发现的几乎所有已知的基因组和细胞遗传学变化的转化浆细胞的克隆性扩增可以在癌前病变(MGUS)患者的临床上保持较长时间的稳定。我们的初步研究表明，这些患者对肿瘤床上的肿瘤细胞产生了强烈而特异的免疫反应，这在骨髓瘤患者中是没有的。我们的假设是，宿主免疫反应在控制患者肿瘤细胞的恶性生长中起着关键作用，并且这种反应严重依赖于体内肿瘤-树突状细胞-T细胞相互作用的背景。MGUS-骨髓瘤是研究肿瘤-免疫相互作用的一个特别有用的模型，因为在这种肿瘤中，可以直接从骨髓肿瘤床中分离出肿瘤和免疫效应细胞和抗原提呈细胞，而不需要体外培养和酶治疗。我们的长期目标是学会利用宿主免疫反应，试图防止MGUS进展为骨髓瘤。我们的具体目标是1)研究骨髓瘤和MGUS患者血液和肿瘤床中宿主抗肿瘤CD4+和CD8+T细胞反应的性质；2)表征肿瘤床中抗原提呈细胞的性质及其与肿瘤细胞的原位相互作用；以及3)研究特定的肿瘤细胞亚群是否可以特异性地靶向树突状细胞，这是人体的天然佐剂。这些研究将为肿瘤微环境中肿瘤细胞和免疫系统之间的相互作用提供新的信息；并建议以树突状细胞为靶点的患者提高抗肿瘤免疫的新策略。