The Tumor Microenvironment Niche of Type I conventional Dendritic Cells

I型常规树突状细胞的肿瘤微环境生态位

• 批准号: 10660263
• 负责人: MATTHEW F KRUMMEL
• 金额: $ 53.11万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-21 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10660263
• 关键词: Acinar Cell; Ally; Animals; Area; Biology; Blocking Antibodies; CD8-Positive T-Lymphocytes; CD8B1 gene; Cell Separation; Cell physiology; Cells; Cellular biology; Collection; Competence; Data Set; Dendritic Cells; Diagnostic; Disease; Endothelium; Engineering; Epithelium; FLT3 ligand; Fibroblasts; Funding; Gene Expression; Genes; Genetic; Goals; Grouping; Growth; Growth Factor; Human; Image; Immune; Immune response; Immune system; Immunity; Immunoassay; Immunologics; Immunotherapy; In Vitro; Knock-out; Lead; Length; Ligands; Light; Liver; Location; Macrophage; Malignant Neoplasms; Mediating; Methods; Migration Assay; Molecular; Natural Killer Cells; Pancreas; Patients; Pattern; Phenotype; Population; Positioning Attribute; Reagent; Research Personnel; Role; Signal Pathway; Specific qualifier value; Stromal Cells; Systems Biology; T-Cell Activation; T-Lymphocyte; Testing; Tissues; Tumor Antigens; Tumor Immunity; Viral; Work; cell motility; cell type; comparison control; design; gene network; human disease; human model; immune checkpoint blockade; interest; intestinal villi; islet; lymph nodes; macrophage-derived chemokine; melanoma; monocyte; mouse model; programs; recruit; response; spatiotemporal; tool; transcriptomics; tumor; tumor microenvironment

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.

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。

项目成果

Archetypes of checkpoint-responsive immunity.

• DOI: 10.1016/j.it.2021.09.007
• 发表时间: 2021-11
• 期刊: Trends in immunology
• 影响因子: 16.8
• 作者: Im K;Combes AJ;Spitzer MH;Satpathy AT;Krummel MF
• 通讯作者: Krummel MF

Uptake of tumor-derived microparticles induces metabolic reprogramming of macrophages in the early metastatic lung.

• DOI: 10.1016/j.celrep.2023.112582
• 发表时间: 2023-06-27
• 期刊: Cell reports
• 影响因子: 8.8

DNGR-1 limits Flt3L-mediated antitumor immunity by restraining tumor-infiltrating type I conventional dendritic cells.

• DOI: 10.1136/jitc-2020-002054
• 发表时间: 2021-05
• 期刊: Journal for immunotherapy of cancer
• 影响因子: 10.9
• 作者: Cueto FJ;Del Fresno C;Brandi P;Combes AJ;Hernández-García E;Sánchez-Paulete AR;Enamorado M;Bromley CP;Gomez MJ;Conde-Garrosa R;Mañes S;Zelenay S;Melero I;Iborra S;Krummel MF;Sancho D
• 通讯作者: Sancho D

SCENITH: A Flow Cytometry-Based Method to Functionally Profile Energy Metabolism with Single-Cell Resolution.

• DOI: 10.1016/j.cmet.2020.11.007
• 发表时间: 2020-12-01
• 期刊: Cell metabolism
• 影响因子: 29
• 作者: Argüello RJ;Combes AJ;Char R;Gigan JP;Baaziz AI;Bousiquot E;Camosseto V;Samad B;Tsui J;Yan P;Boissonneau S;Figarella-Branger D;Gatti E;Tabouret E;Krummel MF;Pierre P
• 通讯作者: Pierre P

Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells.

• DOI: 10.1038/s41467-022-32849-1
• 发表时间: 2022-09-02
• 期刊: Nature communications
• 影响因子: 16.6