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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要这项研究调查了肿瘤中的“反应性”免疫系统，即细胞和分子盟友使免疫疗法发挥作用在本次资助的上一个周期中，我们发现了一组瘤内疗法。 1 型树突状细胞 (cDC1) 将肿瘤抗原呈递给 T 细胞，自然杀伤细胞为 T 细胞提供关键的 Flt3L 反应性肿瘤微环境中的 cDC1 细胞该提案的总体假设是反应性的。肿瘤免疫基于 CD8 T 细胞和那些 cDC1，有一个原型和一个利基——细胞的集合通过定义这些细胞、它们的相关基因及其关系，我们可以了解组织和支持它的类型。将能够更好地创造这个利基，从而实现肿瘤清除。该程序在将空间转录组学与遗传工具和传统细胞技术一起应用方面是独一无二的免疫分析方法了解关键 CDC 之间的关键表型-生物学关系由此产生的发现将有助于设计新的方法来增强抗病毒能力。肿瘤免疫。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Multimodal identification of rare potent effector CD8 T cells in solid tumors.

实体瘤中罕见的有效效应 CD8 T 细胞的多模式鉴定。

DOI：
发表时间：
2023-09-28
期刊：
影响因子：
0
作者：
Ray, Arja;Bassette, Molly;Hu, Kenneth H;Pass, Lomax F;Samad, Bushra;Combes, Alexis;Johri, Vrinda;Davidson, Brittany;Hernandez, Grace;Zaleta;Krummel, Matthew F
通讯作者：
Krummel, Matthew F

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

肿瘤来源的微粒的摄取诱导早期转移性肺中巨噬细胞的代谢重编程。

DOI：
发表时间：
2023-06-27
期刊：
影响因子：
8.8
作者：
Kersten, Kelly;You, Ran;Liang, Sophia;Tharp, Kevin M;Pollack, Joshua;Weaver, Valerie M;Krummel, Matthew F;Headley, Mark B
通讯作者：
Headley, Mark B

Critical role of CD206+ macrophages in organizing anti-tumor immunity.

CD206 巨噬细胞在组织抗肿瘤免疫中的关键作用。

DOI：
发表时间：
2023-11-02
期刊：
影响因子：
0
作者：
Ray, Arja;Hu, Kenneth H;Kersten, Kelly;Kuhn, Nicholas F;Samad, Bushra;Combes, Alexis J;Krummel, Matthew F
通讯作者：
Krummel, Matthew F

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

不同的代谢状态引导炎症和耐受性树突细胞的成熟。

DOI：
发表时间：
2022-09-02
期刊：
影响因子：
16.6
作者：
Adamik, Juraj;Munson, Paul V;Hartmann, Felix J;Combes, Alexis J;Pierre, Philippe;Krummel, Matthew F;Bendall, Sean C;Argüello, Rafael J;Butterfield, Lisa H
通讯作者：
Butterfield, Lisa H

The NK cell-cancer cycle: advances and new challenges in NK cell-based immunotherapies.

NK 细胞-癌症周期：基于 NK 细胞的免疫疗法的进展和新挑战。