Core B: Animal Model and Immunotyping Core

核心 B：动物模型和免疫分型核心

• 批准号: 10493942
• 负责人: Xiaoxia Li
• 金额: $ 39.26万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 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/10493942
• 关键词: Address; Affect; Animal Model; Autologous; Bioinformatics; CD8-Positive T-Lymphocytes; Cancer Model; Cell surface; Cells; Charge; Complement Factor B; 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; Immune; Immune checkpoint inhibitor; Immunocompetent; Immunocompromised Host; Immunotherapy; Individual; Inflammation; Inflammatory; Infrastructure; Interferon-beta; Interferons; Interleukin-17; 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; Suspensions; Testing; Th1 Cells; Therapeutic; Tissues; Transcend; Transforming Growth Factor beta; Transforming Growth Factors; Tumor Biology; Tumor Cell Line; Tumor Immunity; 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; transcriptomics; treatment response; triple-negative invasive breast carcinoma; tumor; tumor microenvironment; tumor progression; tumor xenograft

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.

项目摘要 我们的初步数据表明，STING-IFN-β/TGFβ/IL-17细胞因子的影响有一个共同的模式， 网络上的肿瘤进展和对治疗的反应，这超越了每种癌症的组织起源。 我们的目标是解开串扰并定义范例，这需要协议的标准化， 每个组成项目使用的程序，以统一我们建立临床前肿瘤的方法 模型和测量肿瘤对治疗的反应。我们得出有意义结论的能力 在体内研究的可比执行上。此外，由所有三个组成部分共享的公共读出器可以被配置为： 项目是TME的炎症状态。免疫支持性炎症（CD 8、Th 1和树突状细胞） 细胞）与对免疫检查点抑制剂治疗的有利反应有关，免疫抑制剂是一种免疫抑制剂。 炎性环境（未成熟的骨髓细胞和成纤维细胞）可以拮抗抗肿瘤免疫。 通过流式细胞仪和单细胞仪准确检测、表征和定量多种细胞类型 测序对于评估肿瘤内炎症的状态至关重要。共享基础架构， TME的可靠分析对于研究细胞因子串扰是必要的。总之，动物模型和 免疫分型中心将负责两项任务。首先，核心将提供技术和实验 实现统一和标准体内分析的基础设施，包括癌症的临床前评估 TME的治疗和表征。第二，核心将发挥枢纽作用， 各组成项目，包括分析援助和对TME分析的科学咨询。