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

 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（由申请人提供）：令人遗憾的是，我们不知道哪些宿主细胞在肿瘤中进行培养并对远端部位做出贡献。 此外，尽管特定免疫细胞（例如骨髓细胞）很可能移动到远端淋巴结，但此类细胞的关键特征（其身份寿命、自我更新、特定功能）仍未得到解决。 值得注意的是，我们目前无法知道转移部位的哪些宿主细胞在原发肿瘤中居住后首先到达。在此应用中，我们将开发新技术，在细胞及其后代的整个生命周期中对细胞从一个器官到所有其他器官进行谱系追踪。我们将用它来检验免疫细胞，特别是骨髓谱系的免疫细胞，在以下方面受到“教育”的假设： 肿瘤微环境并有助于远处部位（如淋巴结、脾脏和可能的转移部位）的组成；此外，我们将确定这种贡献的功能后果。值得注意的是，这将代表首次直接且明确地证明哪些细胞运输至引流淋巴结并在引流淋巴结中呈递抗原，对整个谱系进行位点到位点的映射，发现从引流淋巴结中流出的新谱系。 肿瘤和转移部位含有曾经位于另一个病灶内的免疫细胞的测试。该技术解决了现有光切换方法的主要缺陷，并广泛地将尖端实时成像方法扩展到谱系追踪。

项目成果

Spacer-Mediated Control of Coumarin Uncaging for Photocaged Thymidine.

• DOI: 10.1021/acs.joc.9b02617
• 发表时间: 2020-02
• 期刊: The Journal of organic chemistry
• 作者: Shengzhuang Tang;Jayme Cannon;Kelly Yang;M. Krummel;J. R. Baker;S. Choi

Control of an Unusual Photo-Claisen Rearrangement in Coumarin Caged Tamoxifen through an Extended Spacer.

• DOI: 10.1021/acschembio.6b00999
• 发表时间: 2017-04-21
• 期刊: ACS chemical biology
• 影响因子: 4
• 作者: Wong PT;Roberts EW;Tang S;Mukherjee J;Cannon J;Nip AJ;Corbin K;Krummel MF;Choi SK
• 通讯作者: Choi SK

Light-controlled active release of photocaged ciprofloxacin for lipopolysaccharide-targeted drug delivery using dendrimer conjugates.

• DOI: 10.1039/c6cc05179k
• 发表时间: 2016-08-16
• 期刊: Chemical communications (Cambridge, England)
• 作者: Wong PT;Tang S;Mukherjee J;Tang K;Gam K;Isham D;Murat C;Sun R;Baker JR;Choi SK
• 通讯作者: Choi SK

A Thioacetal Photocage Designed for Dual Release: Application in the Quantitation of Therapeutic Release by Synchronous Reporter Decaging.

• DOI: 10.1002/cbic.201600494
• 发表时间: 2017-01-03
• 期刊: CHEMBIOCHEM
• 影响因子: 3.2
• 作者: Wong, Pamela T.;Tang, Shengzhuang;Cannon, Jayme;Mukherjee, Jhindan;Isham, Danielle;Gam, Kristina;Payne, Michael;Yanik, Sean A.;Baker, James R., Jr.;Choi, Seok Ki
• 通讯作者: Choi, Seok Ki