The Tumor Microenvironment Niche of Type I conventional Dendritic Cells

项目总结 这项研究探讨了肿瘤中的“反应性”免疫系统，即 让免疫疗法发挥作用。在前一个周期的资助中，我们发现有一套肿瘤内 树突状细胞1型(CDC1)向T细胞递呈肿瘤抗原，而自然杀伤细胞提供关键的Flt3L 反应性肿瘤微环境中的CDC1细胞。这一提议的总体假设是，反应性 基于CD8T细胞和CDC1T细胞的肿瘤免疫有一个原型和一个利基--一个细胞集合 组织和支持它的类型。通过定义这些细胞、它们的相关基因以及它们之间的关系，我们 将能够更好地创造这一利基，从而实现肿瘤清除。 该程序在应用空间转录学与遗传工具和常规细胞技术方面是独一无二的。 免疫分析方法了解临界CDC之间的临界表型-生物学关系 人口和他们的伴侣。由此产生的发现将对设计新的方法来促进反 肿瘤免疫。

PROJECT SUMMARY This study investigates the ‘reactive’ immune system in tumors, namely the cellular and molecular allies that allow immunotherapies to work. In the previous cycle of this funding, we discovered that one set of intratumoral dendritic cells type 1 (cDC1) present tumor antigens to T cells and that natural killer cells provide critical Flt3L to cDC1 cells within reactive tumor microenvironments. The overall hypothesis of this proposal is that reactive tumor immunity, based on CD8 T cells and those cDC1, has an archetype and a niche—a collection of cell types that organize and support it. By defining those cells, their associated genes and their relationships, we will be in a position to better create this niche and to thus engineer tumor clearance. This program is unique in applying spatial transcriptomics together with genetic tools and conventional cellular immunoassay methods to understand the critical phenotype-biology relationship between critical cDC populations and their partners. The resultant discoveries will be formative for designing new ways to boost anti- tumor immunity.