CUTTING EDGE LINEAGE TRACKING OF TUMOR-EDUCATED IMMUNE CELLS

 描述（由申请人提供）：我们非常不了解哪些宿主细胞在肿瘤中受教育并有助于远端部位。 此外，尽管特异性免疫细胞（例如髓样细胞）很可能行进到远端淋巴结，但这些细胞的关键特征（它们的身份寿命、自我更新、特异性功能）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首先到达原发性肿瘤。在这项应用中，我们将开发新技术，在细胞及其后代的整个生命周期内，从一个器官到所有其他器官追踪细胞的谱系。我们将利用这一点来检验免疫细胞，特别是髓系免疫细胞， 肿瘤微环境，并有助于组成遥远的网站，如淋巴结，脾脏和可能转移的网站;此外，我们将确定这种贡献的功能后果。值得注意的是，这将代表哪些细胞运输到引流淋巴结并在引流淋巴结中呈递抗原的第一个直接和明确的证明，整个谱系的位点到位点的映射，运输出引流淋巴结的新谱系的发现。 肿瘤和转移部位含有曾经在另一个病变内的免疫细胞的测试。该技术解决了现有光开关方法的主要缺陷，并将尖端的实时成像方法广泛扩展到谱系追踪。

 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.