01 - Cancer Biology & Immunology

癌症生物学和免疫学(CBI)计划 概述和目标：癌症生物学和免疫学(CBI)计划的目标是识别基本的 肿瘤细胞生物学和免疫反应机制以开发新的治疗方法 用来治疗癌症。特别是，CBI成员对转录和表观遗传机制感兴趣 控制肿瘤和免疫细胞功能，代谢和代谢产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动中的作用。研究要点：CBI 研究人员最近发现，CXCL12/CXCR4轴是急性髓系白血病的重要靶点 白血病(AML)和慢性粒细胞白血病(CML)。AML靶向CXCR4促进氧化应激 和白血病干细胞的终末分化(细胞代表20201)，而阻断CXCL12结合 使用酪氨酸激酶抑制剂可消除慢性粒细胞白血病干细胞(细胞干细胞20192)。CBI调查人员还定义了 代谢产物如何影响肿瘤和免疫细胞活性：肿瘤衍生的L-2-羟基戊二酸对肾脏的影响 癌症进展和预后(临床。癌症研究20183)，而α-酮戊二酸调节 CD4T细胞的分化和功能(免疫20174)。CBI调查人员的机械性发现 导致了目前正在进行临床试验的疗法，包括一种治疗多发性硬化症的肝素酶抑制剂 骨髓瘤(血液病20185)和治疗MDS和AML的DNMT1抑制剂(NCT04167917)。计划 活动：CBI通过每月会议、年度务虚会和 研讨会。技术论坛向成员介绍共享资源的新功能和现有功能，以及 成员们的发现通过来自 阿拉巴马州药物发现联盟和奥尼尔投资计划。成员：CBI有来自16个国家的57个成员 部门/部门总共有520万美元的NCI资金和1010万美元的与癌症相关的同行- 审查拨款。在当前周期中，CBI成员发表了693份与癌症有关的出版物，其中39% 是跨计划的，23%是计划内的合作，其中18%是在 影响系数为9或更大。未来方向：根据奥尼尔的战略计划，CBI将专注于角色 肥胖和代谢在调节癌症进展和抗肿瘤免疫反应中的作用。在13个人中 癌症与肥胖有关，CBI的研究人员已经在肿瘤生物学和抗肿瘤免疫方面拥有实力 多发性骨髓瘤、肾癌、乳腺癌和卵巢癌，我们希望这些努力将导致合作， 在下一个资助期提供多项PI赠款。这些癌症与我们社区的目标癌症有重叠之处 外展和参与办公室，部分原因是它们与集水区的相关性。最后，CBI成员将 利用ET开发的成像技术，原位跟踪肿瘤细胞活性和免疫细胞活性。

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.