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-扩展年的研究活动将利用同系小鼠癌症 利用U 54基金建立的模型（项目1，3）和最近的单细胞表观遗传/多组学和空间 在我们中心部署的转录组技术（项目1，2，共享资源核心）， 肿瘤-免疫相互作用的实验和计算建模，对人类肿瘤生物学具有高度的保真度 并且具有丰富的单细胞和空间分辨率。下面我们概述了扩展年的六项主要活动， 由中心研究员领导，为我们U 54提案的原始具体目标做出贡献。 1.黑色素瘤中T细胞、间质和癌细胞共同进化的建模（项目1）。 2.学习基因调控程序管理肿瘤相关的T细胞状态（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视（项目3）。 5.转移谱系对营养梯度反应的组织模拟建模（项目3）。 6.单细胞RNA和ATAC测序数据的计算整合（共享资源核心）。 .

项目成果

Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment.

• DOI: 10.1016/j.cell.2018.05.060
• 发表时间: 2018-08-23
• 期刊: Cell
• 影响因子: 64.5
• 作者: Azizi E;Carr AJ;Plitas G;Cornish AE;Konopacki C;Prabhakaran S;Nainys J;Wu K;Kiseliovas V;Setty M;Choi K;Fromme RM;Dao P;McKenney PT;Wasti RC;Kadaveru K;Mazutis L;Rudensky AY;Pe'er D
• 通讯作者: Pe'er D

A nonimmune function of T cells in promoting lung tumor progression.

• DOI: 10.1084/jem.20170356
• 发表时间: 2017-12-04
• 期刊: The Journal of experimental medicine
• 作者: Green JA;Arpaia N;Schizas M;Dobrin A;Rudensky AY
• 通讯作者: Rudensky AY

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

• DOI: 10.1093/bioinformatics/btad267
• 发表时间: 2023-06-30
• 期刊: Bioinformatics (Oxford, England)

Chromatin states define tumour-specific T cell dysfunction and reprogramming.

• DOI: 10.1038/nature22367
• 发表时间: 2017-05-25
• 期刊: Nature
• 影响因子: 64.8
• 作者: Philip M;Fairchild L;Sun L;Horste EL;Camara S;Shakiba M;Scott AC;Viale A;Lauer P;Merghoub T;Hellmann MD;Wolchok JD;Leslie CS;Schietinger A
• 通讯作者: Schietinger A

Metabolic origins of spatial organization in the tumor microenvironment.

• DOI: 10.1073/pnas.1700600114
• 发表时间: 2017-03-14
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Carmona-Fontaine C;Deforet M;Akkari L;Thompson CB;Joyce JA;Xavier JB
• 通讯作者: Xavier JB