Cancer Immunology

癌症免疫学研究：总结 Hollings癌症中心（HCC）的癌症免疫学（CI）计划旨在揭示免疫系统如何在癌症中发挥作用。 系统识别并杀死肿瘤，并利用这些信息开发有效的免疫肿瘤学（IO） 治疗患者的策略。三个统一的主题促进这些目标：1）免疫疗法; 2）炎症 和耐受性;和3）T细胞生物学。在所有三个领域都取得了显著进展。其中包括发射 并完成第一个1b/2期试验，使用 PD-1拮抗剂和超激动剂重组IL-15的组合，开发阻断PD-1拮抗剂和超激动剂重组IL-15的新型溶瘤剂， PD-1通路是阐明血小板如何通过GARP-TGF β轴钝化T细胞免疫的第一份报告，阐明了 确定CD 38在产生抗肿瘤杂交Th 1/17细胞中的作用，揭示其机制， 获得细胞因子信号传导，并发现用于癌症细胞治疗的高效人CD 26+淋巴细胞。 该计划由两名具有不同基础和临床背景的特殊免疫学家共同领导， 精心构建一个协同计划进行前沿研究：李子海，医学博士，博士是一个董事会认证， 资深医学肿瘤学家和免疫学家，在炎症和耐受方面具有专业知识; Chrystal Paulos博士是 肿瘤免疫学家，在基础T细胞生物学和过继性T细胞转移治疗方面具有专长。有20 来自七个学术部门的项目成员。每年的直接费用供资基数为440万美元， 不包括职业发展和培训赠款。目前有28个与癌症有关的资助项目正在进行， 包括一个新的多机构计划项目（NCI P01 CA 186866）。在当前周期，CI 成员发表了138篇同行评审论文，其中40%是计划内合作，43%是计划间合作。 选择。该计划的研究的特殊影响是突出了20个期刊出版物， 影响因子>10，包括Cancer Discov、Cell Metab、Sci Transl Med、J Clin Invest、Nat Med（2018）、Nat Commun，Nat Struct Mol Biol和Lancet Oncol（2018）。自上次延期以来，合同委员会为下列活动提供了资金： 招募七名新的CI成员，包括一名高级临床科学家（Raymond DuBois，MD，PhD）。他们的重新- cruitment促进了新的制药商发起的临床试验，并提供了大数据分析专业知识。HCC也 支持了一些活动，包括方案间春季联合专题讨论会和多机构再培训， 请客该计划受益于所有HCC共享资源，特别是生物统计学和流式细胞术 & Cell Sorting Shared Resources，增加了第二代流式细胞仪用于高维单细胞分析， 细胞分析，反映了重大的机构投资。随着CI计划的成熟， 由多学科研究人员组成的高效团队，IO的快速进展，新的HCC领导的大力支持- 作为该领域向利用免疫系统治疗癌症的关键转变，CI计划是 在下一个供资周期，所有专题研究领域都将取得强劲进展。

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.