Cancer Immunology

癌症免疫学

• 批准号: 10674510
• 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/10674510
• 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; Intrinsic factor; Leadership; Lesion; Macrophage; 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; Stromal Cells; T cell therapy; T-Lymphocyte; Technology; Testing; Translating; Work; anti-CTLA4; anti-PD-1; anti-PD-L1; cancer care; cancer cell; cancer therapy; chimeric antigen receptor T cells; clinical application; clinical investigation; design; human disease; improved; in silico; innate immune function; innovation; 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.

项目总结/摘要-癌症免疫学（CI）研究 Tisch癌症研究所（TCI）的癌症免疫学（CI）项目由30名成员组成， 有一个共同的目标，即研究免疫介导的失调对免疫系统产生不利影响的前提。 TME。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 获得了880万美元的直接成本资金，NCI支持了250万美元， 500万元的支持。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。 纲领性的。 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.开发模型以逆转免疫功能障碍并恢复免疫平衡;以及 3.接受免疫治疗的癌症患者中的反应相关性。癌症进展 其特征是免疫系统在多个水平上逐渐失调， 不受控制的肿瘤生长虽然T细胞功能障碍的作用是众所周知的， 先天免疫系统被类似地劫持以使肿瘤生长。在这方面，CI计划 成员们专注于确定肿瘤微环境（TME）影响肿瘤微环境的新机制。 先天免疫细胞包括巨噬细胞、树突状细胞和NK细胞的功能，以及肿瘤反应性 T细胞。 因此，CI计划有三个主要的科学目标。第一是确定基因组、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筛选和人类肿瘤病变，以确定免疫相关的新机制/靶点 失调和优先考虑最终在新的临床试验中测试的免疫治疗抗性/应答的靶点 审判第二，慈善社成员努力制定以科学为基础的战略， 目前的免疫学平台，并确定风险和治疗反应的免疫生物标志物。的 总体目标是将发现进展为创新的临床试验，以测试和验证 提出了抵抗和反应的相关性。第三个目标是开发新的临床适用的免疫 有效控制或根除癌症的目标。CI成员以伙伴关系和跨方案方式工作 来验证免疫疗法抵抗的相关性。