Core D: Pathology and BioImaging

核心 D：病理学和生物成像

基本信息

批准号：
10362708
负责人：
CARL D MORRISON
金额：
$ 45.45万
依托单位：
ROSWELL PARK CANCER INSTITUTE CORP
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-03 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10362708
关键词：
Aftercare Animals Archives Biological Assay Bioluminescence Biopsy Blood Vessels CD3 Antigens CD8B1 gene CLIA certified Cell Communication Cell Culture Techniques Cells Clinical Clinical Trials Clonal Expansion Clonality Collection Color Colorectal Comprehensive Cancer Center Computer Assisted Computers DNA sequencing Development Doctor of Philosophy Drug or chemical Tissue Distribution Effector Cell Ensure Epitope spreading Evaluation Exhibits FDA approved Flow Cytometry Fluorescence Microscopy Fluorescent in Situ Hybridization Freezing Genes Genomics Growth Human Image Image Analysis Image Cytometry Immune Immune Response Genes Immunofluorescence Immunologic Immunohistochemistry Immunologics Immunotherapy Infrastructure Ions Kinetics Laboratories Lasers Magnetic Resonance Imaging Measures Microsatellite Instability Mus Mutation Myeloid-derived suppressor cells New York Optics Outcome Ovarian PD-1 blockade PD-1/PD-L1 PTGS2 gene Pathology Patients Pattern Population Process Program Evaluation Protocols documentation Recording of previous events Regimen Regulatory T-Lymphocyte Reporting Reproducibility Research Personnel Resource Sharing Role Sampling Scanning Services Site Source Specimen System T cell infiltration T cell response T-Lymphocyte T-cell diversity Technology Testing Tissue Banks Tissue Procurements Tissues Transcript Tumor Tissue Universities Vaccination Vaccines Work bioimaging chemokine chemokine receptor density design experimental study immune checkpoint immunological intervention immunological status in vivo in vivo imaging innovation lymphoid structures medical schools melanoma morphometry mouse model multimodality novel pathology imaging preclinical study programmed cell death ligand 1 programmed cell death protein 1 programs protein expression sample collection sound tissue culture transcriptome sequencing transcriptomics treatment effect tumor tumor growth tumor microenvironment

Aftercare Animals Archives Biological Assay Bioluminescence Biopsy Blood Vessels CD3 Antigens CD8B1 gene CLIA certified Cell Communication Cell Culture Techniques Cells Clinical Clinical Trials Clonal Expansion Clonality Collection Color Colorectal Comprehensive Cancer Center Computer Assisted Computers DNA sequencing Development Doctor of Philosophy Drug or chemical Tissue Distribution Effector Cell Ensure Epitope spreading Evaluation Exhibits FDA approved Flow Cytometry Fluorescence Microscopy Fluorescent in Situ Hybridization Freezing Genes Genomics Growth Human Image Image Analysis Image Cytometry Immune Immune Response Genes Immunofluorescence Immunologic Immunohistochemistry Immunologics Immunotherapy Infrastructure Ions Kinetics Laboratories Lasers Magnetic Resonance Imaging Measures Microsatellite Instability Mus Mutation Myeloid-derived suppressor cells New York Optics Outcome Ovarian PD-1 blockade PD-1/PD-L1 PTGS2 gene Pathology Patients Pattern Population Process Program Evaluation Protocols documentation Recording of previous events Regimen Regulatory T-Lymphocyte Reporting Reproducibility Research Personnel Resource Sharing Role Sampling Scanning Services Site Source Specimen System T cell infiltration T cell response T-Lymphocyte T-cell diversity Technology Testing Tissue Banks Tissue Procurements Tissues Transcript Tumor Tissue Universities Vaccination Vaccines Work bioimaging chemokine chemokine receptor density design experimental study immune checkpoint immunological intervention immunological status in vivo in vivo imaging innovation lymphoid structures medical schools melanoma morphometry mouse model multimodality novel pathology imaging preclinical study programmed cell death ligand 1 programmed cell death protein 1 programs protein expression sample collection sound tissue culture transcriptome sequencing transcriptomics treatment effect tumor tumor growth tumor microenvironment

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项目摘要

ABSTRACT Core D (Pathology and Bio-Imaging Core), directed by Dr. Morrison, MD, will support this clinically oriented Program by providing comprehensive state-of-the-art evaluation of the immune status of tumor microenvironments (TME), using cutting-edge platforms for comprehensive immune profiling, cell and tissue analysis, imaging and image-analysis. Core D includes the following Aims: Aim 1: Provide infrastructure to collect, process, annotate and archive tumor samples and evaluate the immune status of the TME using comprehensive immune profiling. Our Tissue Procurement Service will help collect fresh, frozen and FFPE tumor specimens from the clinical trials of this Program and tissue banking protocols. OmniSeq and multiplex IHC subcore, will perform immunologic, genomic, and transcriptomic assessment of the immune status of the TME, using CLIA-certified Immune Report Card™ (IRC), to determine: 1) transcript levels of 384 immune genes, 2) mutational burden of each tumor, 3) microsatellite instability, and 4) copy number gain of PD-L1 and PD-L2. We will also evaluate 5) on-treatment changes in TCR beta repertoire, to evaluate evidence of tumor-specific T cell response in the TME and 6) Patterns of expression of PD-1/PD-L1/PD-L2 system and COX2 system in relation to T cell infiltrate and clinical outcomes. Aim 2: Provide state-of-the-art immuno-fluorescence imaging and flow cytometry services to interrogate the spatial effects of chemokine modulating agents on immune cell influx, effector- and immuno-suppressive mechanisms in the TME. It will provide state-of-the-art multicolor flow and imaging cytometry, confocal laser scanning and multicolor fluorescence microscopy, combined with computer morphometry and image analysis. Aim 3 (Sub-Core D3): Perform small animal live imaging to determine the kinetics of tumor growth (bioluminescence) in differentially-treated mice and the kinetics of CTL traffic and accumulation in TME. Programmatic Role and Interactions. With Projects 1, 2 and 3 we will evaluate immune profiles of human colorectal, ovarian and melanoma tumors in the course of patient treatment with chemokine-modulating regimens and/or DC vaccines; determine changes in density, clonality and distribution of CTLs and other immune cells in human and mouse tumors treated by CKM in the absence and presence of vaccination and PD-1 blockade, and determine growth kinetics of the differentially treated and non-treated tumors in murine models. We will also determine the impact of treatments on vascular normalization; and formation of tumor- associated lymphoid structures implicated in epitope spreading and long term-treatment effects. Core D will interact with Core A for prioritization of services, with Core B to assure that proper design of studies and sound statistical evaluation of the results. We will work closely with Core C to ensure failsafe procurement of all specimens from the clinical trials, samples annotation and evaluation in context of clinical outcomes.

抽象的由医学博士导演的核心D（病理和生物成像核心）将支持这种面向临床的通过对肿瘤免疫学状况的全面评估来提供计划微环境（TME），使用尖端平台进行全面的免疫分析，细胞和组织分析，成像和图像分析。核心D包括以下目的：目标1：提供基础设施来收集，处理，注释和存档肿瘤样本，并评估 TME的免疫状态使用全面的免疫分析。我们的组织采购服务将帮助从该程序和组织库的临床试验中收集新鲜，冷冻和FFPE肿瘤标本协议。 Omniseq和Multiplex IHC子核心将执行免疫学，基因组和转录组学使用CLIA认证的免疫报告卡™（IRC）评估TME的免疫状态，以确定： 1）384个免疫原的转录水平，2）每个肿瘤的突变伯嫩，3）微卫星不稳定性和 4）PD-L1和PD-L2的拷贝数增益。我们还将评估5）TCR Beta的治疗变化曲目，评估TME中肿瘤特异性T细胞反应的证据和6）表达模式 PD-1/PD-L1/PD-L2系统和COX2系统与T细胞浸润和临床结果有关。 AIM 2：提供最先进的免疫荧光成像和流式细胞仪服务以询问趋化因子调节剂对免疫细胞影响，效应和免疫抑制的空间作用 TME中的机制。它将提供最先进的多色流和成像细胞术，共聚焦激光器扫描和多色荧光显微镜，结合计算机形态计量学和图像分析。 AIM 3（亚核D3）：执行小动物活成像以确定肿瘤生长的动力学（生物发光）在差异治疗的小鼠中以及CTL流量和TME积累的动力学。编程角色和互动。通过项目1、2和3，我们将评估人类的免疫学概况在趋化因子调节的患者治疗过程中，结直肠癌，卵巢和黑色素瘤肿瘤方案和/或直流疫苗；确定CTL和其他的密度，克隆性和分布的变化在不存在和存在疫苗接种和存在的情况下，由CKM治疗的人和小鼠肿瘤中的免疫细胞 PD-1桶，并确定鼠类中不同处理和未处理的肿瘤的生长动力学型号。我们还将确定治疗对血管归一化的影响；和肿瘤的形成相关的淋巴结构在表位扩散和长期治疗效应中实现。核心D会与核心A相互作用以优先提供服务，核心B确保适当的研究和声音设计结果的统计评估。我们将与Core C紧密合作，以确保所有人的故障安全采购临床试验的标本，在临床结果的背景下进行样本注释和评估。