Systems biology of the tumor immune microenvironment

肿瘤免疫微环境的系统生物学

• 批准号: 10415307
• 负责人: Christina S Leslie
• 金额: $ 33.09万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10415307
• 关键词: Cancer Model; Cells; Communication; Computer Models; Epigenetic Process; Evolution; Experimental Models; Funding; Human; Immune; Immunologic Surveillance; Learning; Lung Adenocarcinoma; Mediating; Modeling; Mus; Neoplasm Metastasis; Nutrient; RNA; Regulator Genes; Regulatory T-Lymphocyte; Research Activity; Research Personnel; Research Project Summaries; Resolution; Resource Sharing; Stromal Cells; Systems Biology; T-Lymphocyte; Technology; Tissues; Tumor Biology; XCL1 gene; cancer cell; data sharing networks; melanoma; mimetics; multiple omics; programs; response; transcriptomics; tumor; tumor-immune system interactions

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). .

肿瘤免疫微环境的系统生物学 项目摘要-延长一年的研究活动将利用同基因小鼠癌症 U54 资助建立的模型（项目 1、3）和最近的单细胞表观遗传/多组学和空间模型 我们中心部署的转录组技术（项目 1、2、共享资源核心），使 高保真人类肿瘤生物学的肿瘤免疫相互作用的实验和计算模型 并具有丰富的单细胞和空间分辨率。下面我们概述了延长年的六项主要活动，每项活动 由一名中心研究员领导，为我们 U54 提案的最初具体目标做出贡献。 1. 黑色素瘤中 T 细胞、基质细胞和癌细胞共同进化的建模（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. 肺腺癌中 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中转移的免疫监测（项目3）。 5. 转移谱系对营养梯度响应的组织模拟模型（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）。 。

项目成果

The effect of cellular context on miR-155-mediated gene regulation in four major immune cell types.

细胞环境对四种主要免疫细胞类型中 miR-155 介导的基因调控的影响。

• 发表时间: 2018-10
• 影响因子: 30.5
• 作者: Hsin, Jing;Lu, Yuheng;Loeb, Gabriel B;Leslie, Christina S;Rudensky, Alexander Y
• 通讯作者: Rudensky, Alexander Y

Natural Genetic Variation Reveals Key Features of Epigenetic and Transcriptional Memory in Virus-Specific CD8 T Cells.

自然遗传变异揭示了病毒特异性 CD8 T 细胞表观遗传和转录记忆的关键特征。

• 发表时间: 2019
• 影响因子: 32.4
• 作者: van der Veeken, Joris;Zhong, Yi;Sharma, Roshan;Mazutis, Linas;Dao, Phuong;Pe'er, Dana;Leslie, Christina S;Rudensky, Alexander Y
• 通讯作者: Rudensky, Alexander Y

Metabolic origins of spatial organization in the tumor microenvironment.

肿瘤微环境中空间组织的代谢起源。

• 发表时间: 2017-03-14
• 影响因子: 11.1
• 作者: Carmona;Deforet, Maxime;Akkari, Leila;Thompson, Craig B;Joyce, Johanna A;Xavier, Joao B
• 通讯作者: Xavier, Joao B

scKINETICS: inference of regulatory velocity with single-cell transcriptomics data.

scKINETICS：用单细胞转录组数据推断调节速度。

• 发表时间: 2023-06-30
• 作者: Burdziak, Cassandra;Zhao, Chujun Julia;Haviv, Doron;Alonso;Lowe, Scott W;Pe'er, Dana
• 通讯作者: Pe'er, Dana

Negative Co-stimulation Constrains T Cell Differentiation by Imposing Boundaries on Possible Cell States.

负共刺激通过对可能的细胞状态施加边界来限制 T 细胞分化。

• 发表时间: 2019
• 影响因子: 32.4
• 作者: Wei, Spencer C;Sharma, Roshan;Anang, Nana;Levine, Jacob H;Zhao, Yang;Mancuso, James J;Setty, Manu;Sharma, Padmanee;Wang, Jing;Pe'er, Dana;Allison, James P
• 通讯作者: Allison, James P