Systems biology of the tumor immune microenvironment

肿瘤免疫微环境的系统生物学 项目摘要-建议延长一年的研究活动将利用同基因小鼠癌症 用U54资助建立的模型(项目1、3)和最近的单细胞表观遗传/多组体和空间 在我们中心部署的转录技术(项目1、2、共享资源核心)，支持 高保真的肿瘤-免疫相互作用的实验和计算模型 并且具有丰富的单细胞和空间分辨率。下面我们概述了延展年的六项主要活动，每项活动 由一名中心研究人员领导，并为我们U54提案的最初具体目标做出贡献。 1.模拟黑色素瘤中T细胞、间质和癌细胞的共同进化(项目1)。 2.学习控制肿瘤相关T细胞状态的基因调控程序(项目1)。 3.肺腺癌Treg细胞介导的细胞通讯的空间分析 微环境(项目2)。 4.同基因小鼠肺腺癌模型转移的免疫监测(项目3)。 5.转移谱系对营养梯度反应的组织模拟模型(项目3)。 6.单细胞RNA和ATAC测序数据的计算集成(共享资源核心)。 。

Systems biology of the tumor immune microenvironment Project Summary- Research activities proposed for the extension year will exploit syngeneic murine cancer models established with U54 funding (Projects 1, 3) and recent single cell epigenetic/multiomic and spatial transcriptomic technologies deployed at our Center (Projects 1, 2, Shared Resource Core), enabling experimental and computational modeling of tumor-immune interactions with high fidelity to human tumor biology and at rich single cell and spatial resolution. Below we outline six major activities for the extension year, each led by a Center investigator and contributing to the original specific aims of our U54 proposal. 1. Modeling T cell, stromal, and cancer cell co-evolution in melanoma (Project 1). 2. Learning gene regulatory programs governing tumor-associated T cell states (Project 1). 3. Spatial analyses of Treg cell-mediated cellular communications in the lung adenocarcinoma microenvironment (Project 2). 4. Immune surveillance of metastasis in a syngeneic murine lung adenocarcinoma model (Project 3). 5. Tissue mimetic modeling of the response of metastatic lineages to nutrient gradients (Project 3). 6. Computational integration of single cell RNA and ATAC sequencing data (Shared Resource Core). .