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Core B: Animal Model and Immunotyping Core

核心 B：动物模型和免疫分型核心

基本信息

批准号：
10704234
负责人：
THOMAS A. HAMILTON
金额：
$ 38.49万
依托单位：
CLEVELAND CLINIC LERNER COM-CWRU
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-13 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10704234
关键词：
Address Affect Animal Model Autologous Bioinformatics CD8-Positive T-Lymphocytes Cancer Model Cell surface Cells Charge Consultations Crossbreeding Cytokine Network Pathway Cytokine Signaling Data Data Analyses Dendritic Cells Detection Dissection Dose Ensure Fibroblasts Flow Cytometry Fluorescence-Activated Cell Sorting Fostering Genetically Engineered Mouse Goals Growth Head and Neck Squamous Cell Carcinoma Human IL17 gene Immune Immune checkpoint inhibitor Immunocompetent Immunocompromised Host Immunotherapy Individual Inflammation Inflammatory Infrastructure Interferon-beta Interferons KRASG12D Kinetics Knock-in Mouse Libraries Lung Adenocarcinoma Malignant Neoplasms Malignant neoplasm of lung Measures Mission Modeling Molecular Mouse Strains Mus Myeloid Cells Outcome Pathway interactions Peripheral Blood Mononuclear Cell Procedures Protocols documentation Research Personnel Resistance Role STAT2 gene Sampling Services Shapes Signal Pathway Standardization Sting Injury Suspensions Testing Th1 Cells Therapeutic Tissues Transcend Transforming Growth Factor beta Tumor Biology Tumor Cell Line Tumor Immunity Tumor Promotion Tumor Tissue Work Xenograft Model cancer type cell type checkpoint therapy chemotherapy cytokine design experience experimental study fluorophore humanized mouse immune checkpoint blockade improved in vivo inflammatory milieu instrumentation member mouse model novel therapeutic intervention patient derived xenograft model pre-clinical pre-clinical assessment programs response single cell sequencing tissue preparation tool transcriptome sequencing transcriptomics treatment response triple-negative invasive breast carcinoma tumor tumor microenvironment tumor progression tumor xenograft

项目摘要

Project Summary Our preliminary data suggested a shared paradigm for the impact of the STING-IFN-β/TGFβ/IL-17 cytokine network on tumor progression and responses to therapy, which transcends the tissue origins of each cancer. Our goal, to unravel the crosstalk and define the paradigms, necessitates standardization of the protocols and procedures used by each constituent project, in order to unify our approaches in establishing preclinical tumor models and measuring tumor responses to therapy. Our ability to reach meaningful conclusions critically hinges on comparable execution of in vivo studies. Furthermore, a common readout shared by all three constituent projects is the inflammatory status in the TME. While immune-supportive inflammation (CD8, Th1, and dendritic cells) is associated with favorable responses to immune checkpoint inhibitor therapy, an immune-suppressive inflammatory environment (immature myeloid cells and fibroblasts) can antagonize anti-tumor immunity. Accurate detection, characterization and quantification of multiple cell types by flow cytometry and single-cell sequencing are crucial for assessing the state of intra-tumoral inflammation. A shared infrastructure that enables reliable analysis of the TME is essential for studying cytokine crosstalk. Taken together, the Animal Model and Immunotyping Core will be charged with two missions. First, the Core will provide technical and experimental infrastructure to enable uniform and standard in vivo analyses, including preclinical assessment of cancer therapeutics and characterization of the TME. Secondly, the Core will function as a hub for interaction among the constituent projects, including analytics assistance and scientific consultation on analyses of the TME.

项目总结