Cancer Immunology

癌症免疫学

基本信息

批准号：
10454170
负责人：
Nina Bhardwaj
金额：
$ 2.63万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10454170
关键词：
Animal Model Award Biological Models CRISPR screen Cancer Center Support Grant Cancer Patient Cells Cellular Indexing of Transcriptomes and Epitopes by Sequencing Clinical Trials Clustered Regularly Interspaced Short Palindromic Repeats Dendritic Cells Development Direct Costs Doctor of Philosophy Elements Equilibrium Functional disorder Funding Genomics Goals Human Immune Immune System Diseases Immune Targeting Immune checkpoint inhibitor Immune response Immune system Immunologic Markers Immunology Immunotherapeutic agent Immunotherapy Innate Immune System Institutes Intrinsic factor Leadership Lesion Malignant Neoplasms Mediating Modeling Molecular Myeloid-derived suppressor cells Natural Killer Cells Paper Pathway interactions Patients Peer Review Population Pre-Clinical Model Publishing Refractory Research Personnel Resistance Risk Role Sampling Second Primary Cancers Stromal Cells T cell therapy T-Lymphocyte Technology Testing Translating Work anti-CTLA4 anti-PD-1 anti-PD-L1 base cancer care cancer cell cancer therapy chimeric antigen receptor T cells clinical application clinical investigation cohesion design human disease improved in silico innate immune function innovation macrophage medical schools member novel pre-clinical programs recruit response response biomarker single cell sequencing treatment response tumor tumor growth tumor immunology tumor microenvironment tumor progression

项目摘要

PROJECT SUMMARY/ABSTRACT – CANCER IMMUNOLOGY (CI) PROGRAM The Cancer Immunology (CI) Program of The Tisch Cancer Institute (TCI) is comprised of 30 members who share a common goal to investigate the premise that immune-mediated dysregulation adversely impacts the TME. They represent 15 Departments and 7 Institutes. As of February 2019, CI program members were awarded $8.8 million in direct cost funding, with NCI support of $2.5 million and peer-reviewed cancer related support of $5 million. In 2018, the program published 72 papers of which 30% were intra- and 18% were inter- programmatic. The major scientific themes of the CI program are to investigate: 1. Immune dysregulation in the Tumor Microenvironment (TME); 2. Develop models to reverse immune dysfunction and restore immune balance; and 3. Validate correlates of response in cancer patients receiving immunotherapy. Cancer progression is characterized by gradual dysregulation of the immune system at multiple levels that directly contributes to unchecked tumor growth. While the role of T cell dysfunction is well acknowledged, evidence is accumulating that the innate immune system is analogously hijacked to enable tumor growth. In this regard, CI Program members are focused on identifying new mechanisms whereby the tumor microenvironment (TME) impacts the function of innate immune cells including macrophages, dendritic cells and NK cells, in addition to tumor-reactive T cells. Accordingly, the CI program has three main scientific goals. The first is to identify genomic, molecular and cellular pathways underlying immune dysfunction in the TME. CI members use preclinical model systems, CRISPR screens and human tumor lesions, to identify novel mechanisms/targets underlying immune dysregulation and prioritize targets of immunotherapy resistance/response ultimately tested in novel clinical trials. Second, CI members strive to develop scientifically based strategies that will improve and/or expand current immunotherapeutic platforms, and identify immune biomarkers of risk and response to treatment. The overarching goal is to progress discoveries that are made into innovative clinical trials to test and validate proposed correlates of resistance and response. A third goal is to develop novel clinically applicable immune targets to effectively control or eradicate cancers. CI members work in partnership and inter-programmatically to validate correlates of resistance to immunotherapy.

项目概要/摘要 – 癌症免疫学 (CI) 项目 Tisch 癌症研究所 (TCI) 的癌症免疫学 (CI) 项目由 30 名成员组成，他们拥有一个共同的目标，即研究免疫介导的失调对机体产生不利影响的前提截至 2019 年 2 月，他们代表 15 个部门和 7 个研究所。获得 880 万美元的直接成本资助，其中 NCI 提供 250 万美元的支持以及经过同行评审的癌症相关资金 2018 年，该项目发表了 72 篇论文，其中 30% 为内部论文，18% 为内部论文。程序化的。 CI 项目的主要科学主题是研究： 1. 肿瘤中的免疫失调微环境（TME）；2.开发逆转免疫功能障碍、恢复免疫平衡的模型； 3. 验证接受免疫治疗的癌症患者的反应的相关性。其特点是免疫系统在多个层面上逐渐失调，直接导致尽管 T 细胞功能障碍的作用已得到广泛认可，但证据正在不断积累。先天免疫系统同样被劫持以促进肿瘤生长。在这方面，CI 计划。成员专注于确定肿瘤微环境（TME）影响肿瘤的新机制除了肿瘤反应性细胞外，先天免疫细胞（包括巨噬细胞、树突状细胞和 NK 细胞）的功能 T细胞。因此，CI 项目有三个主要科学目标，第一个是识别基因组、分子和基因组。 CI 成员使用临床前模型系统来研究细胞潜在途径免疫功能障碍， CRISPR 筛选和人类肿瘤病变，以确定免疫的新机制/靶点最终在临床新颖中测试的免疫治疗耐药性/反应的失调和优先目标其次，CI 成员努力制定基于科学的策略，以改进和/或扩展。当前的免疫治疗平台，并识别风险和治疗反应的免疫生物标志物。总体目标是将发现进展到创新的临床试验中以进行测试和验证提出的耐药性和反应的关联性的第三个目标是开发新的临床适用的免疫。 CI 成员合作并跨项目开展工作，以有效控制或根除癌症为目标。验证免疫治疗耐药性的相关性。