CORE 2: Outreach Core

核心 2：外展核心

基本信息

批准号：
9338205
负责人：
Joao Xavier
金额：
$ 14.22万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9338205
关键词：
Address Adopted Algorithms American Antibodies Area Bioinformatics Biological Cancer Immunology Science Cancer Model Cell Proliferation Cells Clinical Communication Communities Computational Biology Computer Analysis Data Disease Disease Progression Ecosystem Education Education and Outreach Educational workshop Epigenetic Process Geographic Locations Goals Graduate Education Heterogeneity Human Immune Immune Evasion Immune system Immunological Models Immunologics Immunology Immunotherapeutic agent Immunotherapy Innate Immune System International Internships Intervention Investigation Journals Malignant Neoplasms Memorial Sloan-Kettering Cancer Center Methods Modeling Molecular Mus Mutation NCI Center for Cancer Research Natural Killer Cells Neoplasm Metastasis Newsletter Population Property Research Research Personnel Research Project Grants Research Support Resource Sharing Resources Scientist Series Stromal Cells Students System Systems Biology T cell differentiation T-Lymphocyte Technology Testing Training Training Activity Training Programs Tumor Antigens Universities cancer cell cancer immunotherapy cancer initiation cancer therapy cancer type cell type design epigenomics immune checkpoint blockade innovation learning materials live cell imaging medical schools multidisciplinary neoplastic cell next generation novel outreach outreach program patient subsets programs response single cell analysis summer research symposium technology development tool transcriptome sequencing tumor tumor progression tumorigenesis undergraduate education undergraduate student virtual web site

项目摘要

SUMMARY Exciting clinical breakthroughs with checkpoint blockade antibodies and adoptive T cell transfers have transformed the field of cancer immunotherapy, demonstrating the power of harnessing the immune system to eliminate cancer cells. However, fundamental challenges and questions remain. Significant clinical responses have only been observed in a subset of patients and cancer types, and it is currently not known what biological properties of tumors determine clinical responses, nor what strategies to adopt in clinical contexts where current immunotherapies are ineffective. To ultimately address these clinical challenges and to design predictably effective cancer treatments, we must deepen our fundamental understanding of interactions between tumors and the immune system at the molecular, cellular, and systems levels. The CSBC Research Center for Cancer Systems Immunology at MSKCC will bring the tools of systems biology to investigate cancer-immune system interactions at multiple stages of disease progression to answer central questions in cancer immunology and inform the design of novel immunotherapeutic interventions. We have organized our Research Center around three central scientific projects that examine cancer-immune interactions at distinct stages of disease progression: cancer initiation and early tumorigenesis (Project I); established and progressing tumors (Project II); latent disease and metastasis in (Project III). In Project I, we will combine new epigenomics technologies and innovative single-cell analyses with state-of-the-art systems biology approaches to decipher the underlying molecular and epigenetic programs of dysfunctional tumor- specific T cell differentiation in early tumorigenesis. We will further elucidate how dynamics in the mutational tumor antigen landscape and stromal and immune cell populations determine such states and model and test in mouse and human tumors how distinct T cell states determine sensitivity to immune checkpoint blockade. In Project II, we will use quantitative analysis of cell types and cell states by functional, flow cytometric, population RNA-seq and droplet RNA sequencing together with ecological models of cancer, immune, and stromal cell populations to study the response of the tumor ecosystem to immunotherapeutic perturbations in established tumors. In Project III, we will examine the evolutionary dynamics of innate immune system control of metastatic disease, a new area of investigation in cancer immunology. We will investigate the heterogeneity of latent cancer cells in their capacity for immune evasion, and we will use quantitative methods, including live cell imaging, to model latent tumor cell evasion of innate immune control and the dynamics of cycles of latent cell proliferation and potential editing by NK cells. A Shared Resource Core will provide state-of-the-art single-cell droplet sequencing technology and computational analysis of single-cell RNA-seq data (scRNA- seq). This Shared Resource Core will be tasked with droplet sequencing technology development and design of novel algorithmic approaches and will interact with all three scientific Projects. Our Research Center will also carry out an innovative program of outreach and training activities at the local, national, and global levels to disseminate research findings in cancer systems immunology and to train young scientists in this emerging field.

概括检查点阻断抗体和过继性 T 细胞移植取得了令人兴奋的临床突破改变了癌症免疫治疗领域，展示了利用免疫系统来治疗癌症的力量消除癌细胞。然而，根本性的挑战和问题仍然存在。显着的临床反应仅在一部分患者和癌症类型中观察到，目前尚不清楚其生物学意义肿瘤的特性决定了临床反应，也决定了在临床环境中采取什么策略目前的免疫疗法无效。为了最终解决这些临床挑战并设计可预测有效的癌症治疗，我们必须加深对相互作用的基本理解在分子、细胞和系统水平上肿瘤和免疫系统之间的关系。 CSBC 研究 MSKCC 癌症系统免疫学中心将利用系统生物学工具进行研究癌症-免疫系统在疾病进展多个阶段的相互作用，以回答以下核心问题癌症免疫学并为新型免疫治疗干预措施的设计提供信息。我们的研究中心围绕三个检查癌症免疫的中央科学项目进行组织疾病进展不同阶段的相互作用：癌症发生和早期肿瘤发生（项目 I）；已形成和进展的肿瘤（项目 II）；（项目III）中的潜伏性疾病和转移。在项目一中，我们将新的表观基因组学技术和创新的单细胞分析与最先进的系统相结合生物学方法破译功能失调肿瘤的潜在分子和表观遗传程序早期肿瘤发生中的特异性 T 细胞分化。我们将进一步阐明突变的动态肿瘤抗原景观以及基质和免疫细胞群决定了这种状态以及模型和测试在小鼠和人类肿瘤中，不同的 T 细胞状态如何决定对免疫检查点阻断的敏感性。在项目 II，我们将通过功能、流式细胞术、群体 RNA-seq 和液滴 RNA 测序以及癌症、免疫和疾病的生态模型基质细胞群来研究肿瘤生态系统对免疫治疗扰动的反应已形成的肿瘤。在项目 III 中，我们将研究先天免疫系统控制的进化动力学转移性疾病的研究，癌症免疫学的一个新研究领域。我们将研究异质性潜伏癌细胞的免疫逃避能力，我们将使用定量方法，包括活体细胞成像，模拟潜伏肿瘤细胞逃避先天免疫控制和潜伏周期的动态细胞增殖和 NK 细胞的潜在编辑。共享资源核心将提供最先进的单细胞液滴测序技术和单细胞RNA-seq数据的计算分析（scRNA- 序列）。该共享资源核心将负责液滴测序技术的开发和设计新颖的算法方法并将与所有三个科学项目互动。我们的研究中心还将在当地开展创新的外展和培训活动计划，国家和全球层面传播癌症系统免疫学研究成果并培训年轻人这个新兴领域的科学家。