Cancer Immunology

癌症免疫学

• 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
• 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

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）计划 Tisch癌症研究所（TCI）的癌症免疫学（CI）计划完成了30名成员 分享一个共同的目标，以调查免疫介导的失调不利影响的前提 TME。他们代表15个部门和7个机构。截至2019年2月，CI计划成员是 授予880万美元的直接成本资金，NCI支持250万美元，并与同行评审的癌症有关 支持500万美元。 2018年，该计划发表了72篇论文，其中30％为内部，18％的论文为中 程序化。 CI计划的主要科学主题是研究：1。肿瘤中的免疫失调 微环境（TME）； 2。开发模型以逆转免疫功能障碍并恢复免疫电极平衡；和 3。验证接受免疫疗法的癌症患者的反应对应关系。癌症的进展是 以多个级别的多个级别的等级失调为特征，直接有助于 未检查的肿瘤生长。虽然T细胞功能障碍的作用得到了很好的认可，但证据正在积累 先天免疫系统被类似地劫持以实现肿瘤生长。在这方面，CI计划 成员专注于确定肿瘤微环境（TME）影响的新机制 除肿瘤反应性外 T细胞。 彼此之间，CI计划具有三个主要的科学目标。首先是鉴定基因组，分子和 TME中免疫功能障碍的细胞途径。 CI成员使用临床前模型系统， CRISPR屏幕和人类肿瘤病变，以识别免疫免疫的新机制/靶标 失调和优先考虑免疫疗法抗性/反应的靶标最终在新型临床中测试 试验。其次，CI成员努力制定基于科学的策略，以改善和/或扩展 当前的免疫治疗平台，并确定风险和对治疗反应的免疫生物标志物。 总体目标是进步进入创新临床试验中的发现，以测试和验证 建议的抗性和反应相关。第三个目标是开发新颖的临床适用免疫 有效控制或放射线取消器的目标。 CI成员通过合作伙伴关系和程序间工作 验证与免疫疗法抗性的相关性。