CORE 2: Outreach Core

核心 2：外展核心

• 批准号: 9980807
• 负责人: Joao Xavier
• 金额: $ 16.66万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-26 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9980807
• 关键词: Address; Adopted; Algorithms; American; Antibodies; Area; Bioinformatics; Biological; 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; 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 cell therapy; T-Lymphocyte; Technology; Testing; Training; Training Activity; Tumor Antigens; Universities; cancer cell; cancer immunotherapy; cancer initiation; cancer therapy; cancer type; cell type; design; droplet sequencing; 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; single-cell RNA sequencing; summer research; symposium; technology development; tool; transcriptome sequencing; tumor; tumor immunology; tumor progression; tumorigenesis; undergraduate education; undergraduate student; virtual; web site

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 具有检查点封闭抗体和收养T细胞转移的令人兴奋的临床突破 改变了癌症免疫疗法领域，证明了利用免疫系统的力量 消除癌细胞。但是，仍然存在基本挑战和问题。显着的临床反应 仅在一部分患者和癌症类型中观察到，目前尚不知道什么生物学 肿瘤的特性决定了临床反应，也决定在临床环境中采用哪些策略 当前的免疫疗法无效。最终应对这些临床挑战并设计 可以预见的有效癌症治疗，我们必须加深对互动的基本理解 在分子，细胞和系统水平的肿瘤和免疫系统之间。 CSBC研究 MSKCC癌症系统免疫学中心将带来系统生物学的工具来调查 疾病进展的多个阶段的癌症免疫系统相互作用，以回答中心问题 癌症免疫学并为新型免疫治疗干预措施设计。 我们已经组织了研究中心，围绕三个中心科学项目，检查癌症免疫 在疾病进展的不同阶段的相互作用：癌症的启动和早期肿瘤发生（项目I）； 建立和进展的肿瘤（项目II）； （项目III）中的潜在疾病和转移。在项目I中，我们 将结合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 生物学方法是破译功能失调肿瘤的基本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中的动态 肿瘤抗原景观以及基质和免疫细胞种群决定了这种状态，模型和测试 在小鼠和人类肿瘤中，不同的T细胞状态如何确定对免疫检查点阻滞的敏感性。在 项目II，我们将通过功能，流式细胞仪对细胞类型和细胞态进行定量分析， 种群RNA-seq和液滴RNA测序以及癌症，免疫和生态模型 基质细胞种群研究肿瘤生态系统对免疫治疗性扰动的反应 已建立的肿瘤。在项目III中，我们将研究先天免疫系统控制的进化动力 转移性疾病，这是一个新的癌症免疫学调查领域。我们将研究异质性 潜在的癌细胞以其免疫逃避的能力，我们将使用定量方法，包括实时 细胞成像，以模拟先天免疫控制的潜在肿瘤细胞逃避和潜在的循环动力学 NK细胞的细胞增殖和潜在编辑。共享资源核心将提供最新的 单细胞测序技术和单细胞RNA-seq数据的计算分析（SCRNA- SEQ）。该共享资源核心将负责液滴测序技术开发和设计 新颖的算法方法，将与所有三个科学项目互动。 我们的研究中心还将在当地的当地进行外展和培训活动的创新计划 在癌症系统免疫学中传播研究结果并培训年轻的国家和全球级别 这个新兴领域的科学家。