CUTTING EDGE LINEAGE TRACKING OF TUMOR-EDUCATED IMMUNE CELLS

肿瘤免疫细胞的尖端谱系追踪

• 批准号: 8990830
• 负责人: MATTHEW F KRUMMEL
• 金额: $ 17.12万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8990830
• 关键词: Accounting; Address; Antigens; Area; Bone Marrow; Cells; Cessation of life; Complement; Development; Disease; Distal; Distant; Environment; Goals; Grant; Health; Human; Image; Imaging technology; Immune; Immunity; Immunologic Surveillance; Immunosuppressive Agents; Label; Lead; Lesion; Life; Light; Location; Longevity; Lung; Lymphoid; Lymphoid Cell; Malignant Neoplasms; Maps; Methodology; Methods; Modeling; Myelogenous; Myeloid Cells; National Institute of Allergy and Infectious Disease; Neoplasm Metastasis; Organ; Pathway interactions; Peripheral; Primary Neoplasm; Risk; Seeds; Site; Specificity; Spleen; T-Lymphocyte Subsets; Techniques; Technology; Testing; Tissues; Travel; Variant; adaptive immunity; anticancer research; cell motility; cell type; chemical genetics; controlled release; in vivo; injury and repair; innovation; lymph nodes; neoplastic cell; new technology; novel; residence; self-renewal; tool; trafficking; tumor; tumor microenvironment; Accounting; Address; Antigens; Area; Bone Marrow; Cells; Cessation of life; Complement; Development; Disease; Distal; Distant; Environment; Goals; Grant; Health; Human; Image; Imaging technology; Immune; Immunity; Immunologic Surveillance; Immunosuppressive Agents; Label; Lead; Lesion; Life; Light; Location; Longevity; Lung; Lymphoid; Lymphoid Cell; Malignant Neoplasms; Maps; Methodology; Methods; Modeling; Myelogenous; Myeloid Cells; National Institute of Allergy and Infectious Disease; Neoplasm Metastasis; Organ; Pathway interactions; Peripheral; Primary Neoplasm; Risk; Seeds; Site; Specificity; Spleen; T-Lymphocyte Subsets; Techniques; Technology; Testing; Tissues; Travel; Variant; adaptive immunity; anticancer research; cell motility; cell type; chemical genetics; controlled release; in vivo; injury and repair; innovation; lymph nodes; neoplastic cell; new technology; novel; residence; self-renewal; tool; trafficking; tumor; tumor microenvironment

 DESCRIPTION (provided by applicant): We are woefully ignorant of which host cells are educated in the tumor and contribute to distal sites. Further, although it is very likely that specific immune cells (e.g. myeloid) travel to the distal lymph nodes, key features (their identity lifespan, self-renewal, specific functions) of such cells remains unaddressed. Remarkably, we cannot currently know which host cells in a metastatic site first arrived following residence in a primary tumor. In this application we will develop new technologies to lineage-track cells from one organ to all others, over the entire lifespan of the cell and its progeny. We will use this to test the hypothesis that immune cells, particularly those of the myeloid lineage, are 'educated' in the tumor microenvironment and contribute to the composition of distant sites such as lymph node, spleen and possibly metastatic sites; furthermore we will determine the functional consequences of such a contribution. Notably, this will represent the first direct and unambigious demonstration of which cells traffic to and present antigens in draining lymph nodes, a site-to-site mapping of entire lineages, a discovery of novel lineages that traffic out of tumors and a test that metastatic sites contain immune cells that were once within another lesion. This technology solves a major deficit with existing photoswitchable approaches and broadly extends cutting edge live-imaging approaches towards lineage tracing.

 描述（由适用提供）：我们非常了解哪些宿主细胞在肿瘤中受过教育，并为不同的部位做出贡献。尽管特定的免疫细胞（例如髓样）很可能传播到不同的淋巴结，但此类细胞的关键特征（其身份寿命，自我更新，特定功能）仍然未受补充。值得注意的是，我们目前不知道转移性部位中哪些宿主细胞在原发性肿瘤中首次到达。在此应用中，我们将在整个细胞及其后代的整个生命周期内开发从一个器官到其他所有器官的谱系细胞。我们将使用它来检验以下假设：免疫细胞，尤其是髓样谱系的细胞。 肿瘤微环境并有助于远处位点的组成，例如淋巴结，脾和可能的转移部位；此外，我们将确定这种贡献的功能后果。值得注意的是，这将代表第一个直接且明确的演示，即在排水淋巴结中流动并呈现抗原，这是整个谱系的站点对位置的映射，这是对新型谱系的发现，从 肿瘤和转移部位的测试含有曾经在另一个病变内的免疫细胞。这项技术通过现有的可拍摄方法解决了主要的赤字，并广泛地扩展了沿着谱系追踪的最先进的现场模仿方法。