01 - Cancer Biology & Immunology

01 - 癌症生物学

• 批准号: 10411027
• 负责人: SUNIL SUDARSHAN
• 金额: $ 5.21万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-28 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10411027
• 关键词: ATAC-seq; Abbreviations; Acarbose; Achievement; Acute Myelocytic Leukemia; Alabama; Basic Science; Bioinformatics Shared Resource; Biological Assay; Biometry; Bone Marrow; CD4 Positive T Lymphocytes; CXCL12 gene; CXCR4 gene; Cancer Biology; Cancer Center Support Grant; Cancer Control; Cancer Prognosis; Catchment Area; Cell physiology; Cells; Cellular biology; Chronic Myeloid Leukemia; Clinical Sciences; Clinical Trials; Collaborations; Community Outreach; Comprehensive Cancer Center; Doctor of Philosophy; Epigenetic Process; Exhibits; Flow Cytometry; Funding; Future; Gene Expression; Genetic; Genetic Engineering; Genetic Transcription; Genomics Shared Resource; Goals; Grant; Heparanase inhibitors; Histone Deacetylase; Histone Deacetylase Inhibitor; Imaging Techniques; Immune; Immune response; Immunity; Immunologist; Immunology; Immunology procedure; Impairment; In Situ; Infrastructure; Intestines; Investigational Therapies; Journals; Knowledge; Lead; Leadership; Link; Location; Malignant Neoplasms; Malignant neoplasm of ovary; Mediating; Medicine; Metabolic; Metabolism; Microscopy; Modeling; Multiple Myeloma; Neuroendocrine Tumors; Obesity; Oxidative Stress; Pathway interactions; Peer Review Grants; Pharmaceutical Preparations; Phase I Clinical Trials; Phenotype; Population Sciences; Positron-Emission Tomography; Program Appropriateness; Proteomics Shared Resource; Publications; Publishing; Regulation; Regulatory T-Lymphocyte; Renal Cell Carcinoma; Renal carcinoma; Research; Research Activity; Research Personnel; Resistance; Resource Development; Resource Sharing; Role; Services; Site; Strategic Planning; Surgical Oncologist; Sushi Domain; Technology; Testing; Therapeutic; Tissue Procurements; Training; Training and Education; Transgenic Organisms; Translational Research; Tumor Biology; Tumor Burden; Tumor Cell Biology; Tumor Immunity; Tumor-Derived; Tumor-Infiltrating Lymphocytes; Tumor-infiltrating immune cells; Tyrosine Kinase Inhibitor; Urology; alpha ketoglutarate; animal imaging; anti-tumor immune response; anticancer research; cancer cell; cell type; clinical center; community engagement; drug development; drug discovery; epigenome; high throughput screening; human imaging; inhibitor; interest; leukemic stem cell; malignant breast neoplasm; meetings; member; microbiome; mitochondrial metabolism; neoplastic cell; neuro-oncology; novel strategies; novel therapeutic intervention; novel therapeutics; nutrition; patient derived xenograft model; programs; receptor; single-cell RNA sequencing; stem cells; structural biology; symposium; therapy outcome; tumor; tumor behavior; tumor growth; tumor immunology; tumor metabolism; tumor microenvironment; tumor progression; urologic

ABSTRACT – CANCER BIOLOGY AND IMMUNOLOGY (CBI) PROGRAM Overview and Goals: The goals of the Cancer Biology and Immunology (CBI) program are to identify basic mechanisms of cancer cell biology and the immune response in order to develop novel therapeutic approaches to treat cancer. In particular, CBI members are interested in the transcriptional and epigenetic mechanisms controlling tumor and immune cell function, the impact of metabolism and metabolites on tumor and immune cell biology, and the role of the microenvironment in tumor biology and immune activity. Research Highlights: CBI investigators recently showed that the CXCL12/CXCR4 axis is an important target in both Acute Myeloid Leukemia (AML) and Chronic Myeloid Leukemia (CML). Targeting CXCR4 on AML promotes oxidative stress and terminal differentiation of leukemic stem cells (Cell Rep. 20201), whereas blockade of CXCL12 combined with tyrosine kinase inhibitors eliminates CML stem cells (Cell Stem Cell 20192). CBI investigators also defined how metabolites influence tumor and immune cell activities: tumor-derived L-2-hydroxyglutarate influences renal cancer progression and prognosis (Clin. Cancer Res. 20183), and alpha-ketoglutarate regulates the differentiation and function of CD4 T cells (Immunity 20174). Mechanistic discoveries by CBI investigators have led to therapeutics that are now being tested in clinical trials, including a heparanase inhibitor for multiple myeloma (Haematologica 20185) and a DNMT1 inhibitor for MDS and AML (NCT04167917). Program Activities: CBI catalyzes intra- and inter-programmatic interactions via monthly meetings, annual retreats, and seminars. Technology forums introduce members to new and existing capabilities of the Shared Resources, and members' discoveries are advanced from the bench to Phase I clinical trials through pilot funding from the Alabama Drug Discovery Alliance and the O'Neal Invests program. Members: CBI has 57 members from 16 Departments/Divisions who have a combined $5.2M in NCI funding and $10.1M in total cancer-relevant, peer- reviewed grants. In the current cycle, CBI members published 693 cancer-relevant publications, of which 39% were inter-programmatic and 23% were intra-programmatic collaborations and 18% of which are in journals with impact factor of 9 or greater. Future Directions: In line with the O'Neal strategic plan, CBI will focus on the role of obesity and metabolism in regulating cancer progression and the anti-tumor immune response. Of the 13 cancers linked with obesity, CBI investigators already have strength in tumor biology and anti-tumor immunity in multiple myeloma, renal, breast, and ovarian cancers, and we expect that these efforts will lead to collaborative, multi-PI grants in the next funding period. These cancers overlap with those being targeted by our Community Outreach and Engagement office, in part due to their relevance to the catchment area. Finally, CBI members will leverage imaging techniques developed by ET to follow tumor cell activity and immune cell reactivity in situ.

摘要 – 癌症生物学和免疫学 (CBI) 项目 概述和目标：癌症生物学和免疫学 (CBI) 计划的目标是确定基本的 癌细胞生物学和免疫反应的机制，以开发新的治疗方法 CBI 成员对治疗癌症尤其感兴趣。 控制肿瘤和免疫细胞功能，代谢和代谢物对肿瘤和免疫细胞的影响 生物学，以及微环境在肿瘤生物学和免疫活性中的作用研究亮点：CBI。 研究人员最近表明，CXCL12/CXCR4 轴是急性髓系白血病的重要靶标。 白血病 (AML) 和慢性粒细胞白血病 (CML) 靶向 CXCR4 可促进氧化应激。 和白血病干细胞的终末分化 (Cell Rep. 20201)，而 CXCL12 的阻断结合 酪氨酸激酶抑制剂可以消除 CML 干细胞（Cell Stem Cell 20192）。 代谢物如何影响肿瘤和免疫细胞活性：肿瘤来源的 L-2-羟基戊二酸影响肾脏 癌症进展和预后（Clin. Cancer Res. 20183），α-酮戊二酸调节 CD4 T 细胞的分化和功能 (Immunity 20174) CBI 研究人员的机制发现。 导致目前正在临床试验中测试的疗法，包括用于多种疾病的乙酰肝素酶抑制剂 骨髓瘤 (Haematologica 20185) 和用于 MDS 和 AML 的 DNMT1 抑制剂 (NCT04167917)。 活动：CBI 通过月度会议、年度务虚会和年度会议来促进计划内和计划间的互动 技术论坛向成员介绍共享资源的新功能和现有功能，以及 通过来自协会的试点资助，成员的发现从实验室推进到第一阶段临床试验 阿拉巴马州药物发现联盟和奥尼尔投资计划成员：CBI 有 16 个成员中的 57 个。 NCI 资助总额为 520 万美元，癌症相关同行资助总额为 1,010 万美元的部门/部门 在当前周期中，CBI 成员发表了 693 篇与癌症相关的出版物，其中 39% 是项目间合作，23% 是项目内合作，其中 18% 是在与 影响因子为9或更高 未来方向：根据奥尼尔的战略计划，CBI将重点关注这个角色。 肥胖和代谢在调节癌症进展和抗肿瘤免疫反应中的作用。 癌症与肥胖有关，CBI 研究人员在肿瘤生物学和抗肿瘤免疫方面已经具备实力 多发性骨髓瘤、肾癌、乳腺癌和卵巢癌，我们期望这些努力将带来协作、 这些癌症与我们社区的目标重叠。 外展和参与办公室，部分原因是其与服务区域的相关性。最后，CBI 成员将。 利用 ET 开发的成像技术来原位追踪肿瘤细胞活性和免疫细胞反应性。