Cancer Immunology

癌症免疫学项目：综述 霍林斯癌症中心的癌症免疫学(CI)项目试图揭示免疫系统是如何 系统识别和杀死肿瘤，并利用这些信息开发有效的免疫肿瘤学(IO) 治疗病人的策略。三个统一的主题促进了这些目标：1)免疫治疗；2)炎症 和耐受性；3)T细胞生物学。这三个领域都取得了显著进展。这包括发射 和完成第一阶段1b/2试验，使用 PD-1拮抗剂和超激动剂重组IL-15的联合应用，开发新型阻断肿瘤的溶瘤剂 PD-1途径首次阐明了血小板如何通过GARP-转化生长因子轴抑制T细胞免疫。 测定CD38在产生抗肿瘤杂合Th1/17细胞中的作用，揭示其作用机制。 包含细胞因子信号，并发现高度有效的人类CD26+淋巴细胞用于癌症的细胞治疗。 该项目由两位具有不同基础和临床背景的杰出免疫学家共同领导，他们共同-- 实验室建立一个进行尖端研究的协同项目：李紫海，医学博士，博士是一个董事会证书-- 在炎症和耐受性方面具有专业知识的医学肿瘤学家和免疫学家；克里斯特尔·保罗博士 在基础T细胞生物学和过继T细胞转移治疗方面具有专业知识的肿瘤免疫学家。有20个 来自七个学术部门的项目成员。每年的资金基数是440万美元的直接成本， 不包括职业发展和培训补助金。有28个活跃的癌症相关资助项目，9个 来自NCI，包括一个新的多机构方案项目(NCI P01 CA186866)。在当前周期中，CI 成员发表了138篇同行评审的论文，其中40%是计划内合作，43%是计划间合作- 特兹。该计划研究的特殊影响通过在期刊上发表的20篇文章来突出，这些期刊包括 影响因素&10包括癌症发现、细胞代谢、科学转化医学、J临床投资、NAT医学(2018)、NAT Commun，Nat Struct Mol Biol和Lancet Onol(2018)。自上次更新以来，肝细胞癌提供了资金 招募7名CI新成员，其中包括一名资深临床医生兼科学家(Raymond DuBois，医学博士)。他们的再- CRUTITION促进了新的研究人员发起的临床试验，并提供了大数据分析专业知识。肝细胞癌也 支持了一些活动，包括方案间联合春季专题讨论会和多机构再培训 招待。该计划受益于所有HCC共享的资源，特别是生物统计学和流式细胞术 &细胞分选共享资源，增加了第二代质量细胞仪，用于高维单细胞 细胞分析，反映了重大的机构投资。随着CI计划的成熟，CI计划将成为一项新的计划-- 多学科调查人员的ERGERGISH团队，IO的快速进展，新的HCC领导的大力支持-- 以及该领域向利用免疫系统治疗癌症的关键转变，CI计划是 准备在下一个供资周期内在所有专题研究领域取得强劲进展。

CANCER IMMUNOLOGY PROGRAM: SUMMARY The Cancer Immunology (CI) Program at the Hollings Cancer Center (HCC) seeks to uncover how the immune system recognizes and kills tumors and to use this information to develop effective immuno-oncology (IO) strategies to treat patients. Three unifying themes promote these goals: 1) immunotherapy; 2) inflammation and tolerance; and 3) T-cell biology. Notable progress has been made in all three areas. This includes launch and completion of the first phase 1b/2 trial on the treatment of advanced non-small cell lung cancer using the combination of a PD-1 antagonist and super-agonist recombinant IL-15, developing novel oncolytics that block the PD-1 pathway, a first report elucidating how platelets blunt T-cell immunity via the GARP-TGF axis, eluci- dating the roles of CD38 in generating the anti-tumor hybrid Th1/17 cells, uncovering the mechanism that sus- tains cytokine signaling, and discovering highly potent human CD26+ lymphocytes for cell therapy of cancer. The program is co-led by two exceptional immunologists with distinct basic and clinical backgrounds who col- laboratively build a synergistic program conducting cutting edge research: Zihai Li, MD, PhD is a board-certi- fied medical oncologist and immunologist with expertise in inflammation and tolerance; Chrystal Paulos, PhD is a tumor immunologist with expertise in basic T-cell biology and adoptive T-cell transfer therapy. There are 20 program members from seven academic departments. The annual funding base is $4.4 million in direct costs, excluding career development and training grants. There are 28 active cancer-related funded projects, nine from the NCI, including a new multi-institutional program project (NCI P01 CA186866). In the current cycle, CI members published 138 peer-reviewed papers, of which 40% are intra- and 43% interprogrammatic collabora- tions. The exceptional impact of the program’s research is highlighted by 20 publications in journals with an impact factor >10 including Cancer Discov, Cell Metab, Sci Transl Med, J Clin Invest, Nat Med (2018), Nat Commun, Nat Struct Mol Biol, and Lancet Oncol (2018). Since the last renewal, the HCC contributed funding to recruit seven new CI members, including one senior clinician-scientist (Raymond DuBois, MD, PhD). Their re- cruitment fostered new investigator-initiated clinical trials and provided big data analysis expertise. HCC also supported a number of events, including inter-programmatic joint spring symposia and multi-institutional re- treats. The program benefits from all HCC shared resources, particularly the Biostatistics and Flow Cytometry & Cell Sorting Shared Resources, which added a 2nd-generation mass cytometer for high-dimensional single- cell analysis, reflecting a significant institutional investment. With the maturation of the CI Program into a syn- ergistic team of multidisciplinary investigators, the rapid progress of IO, strong support from the new HCC lead- ership, and the key shift in the field toward harnessing the immune system to treat cancer, the CI Program is positioned for robust progress in all thematic research areas in the next funding cycle.