Cancer Immunology

癌症免疫学

• 批准号: 10022663
• 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
• 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/10022663
• 关键词: Animal Model; Award; Biological Models; CRISPR screen; Cancer Center Support Grant; Cancer Patient; Cells; 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; Structure; 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

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.

项目摘要/摘要--癌症免疫学(CI)方案 Tisch癌症研究所(TCI)的癌症免疫(CI)计划由30名成员组成，他们 有一个共同的目标，那就是调查免疫介导的调节失调对 我也是。他们代表15个部门和7个研究所。截至2019年2月，CI计划成员为 获得880万美元的直接成本资金，NCI提供250万美元的支持，并与癌症相关的同行审查 500万美元的支持。2018年，该计划发表了72篇论文，其中30%是内部论文，18%是内部论文 程序化的。 CI计划的主要科学主题是调查：1.肿瘤中的免疫失调 微环境(TME)；2.建立逆转免疫功能障碍和恢复免疫平衡的模型；以及 3.验证接受免疫治疗的癌症患者的反应相关因素。癌症的进展是 以免疫系统在多个层次上逐渐失调为特征的，这直接导致 肿瘤肆无忌惮地生长。虽然T细胞功能障碍的作用得到了很好的承认，但证据正在积累 与生俱来的免疫系统被类似地劫持以促进肿瘤的生长。在这方面，CI计划 成员们专注于确定肿瘤微环境(TME)影响肿瘤生长的新机制。 除肿瘤反应外，包括巨噬细胞、树突状细胞和NK细胞在内的天然免疫细胞的功能 T细胞。 因此，CI计划有三个主要的科学目标。第一个是鉴定基因组、分子和 TME中潜在免疫功能障碍的细胞通路。CI成员使用临床前模型系统， CRISPR筛查和人类肿瘤病变，以确定潜在免疫的新机制/靶点 免疫治疗抵抗/反应的失调和优先靶点最终在新的临床试验中得到测试 审判。第二，CI成员努力制定基于科学的战略，以改进和/或扩大 目前的免疫治疗平台，并确定免疫生物标记物的风险和治疗反应。这个 首要目标是将发现进展为创新的临床试验，以进行测试和验证 提出了抵抗力和应答力的相关性。第三个目标是开发可用于临床的新型免疫系统。 有效控制或根除癌症的目标。CI成员以伙伴关系和相互编程的方式工作 验证免疫治疗耐药的相关因素。