Tumor Microenvironment and Cancer Immunology

摘要-肿瘤微环境与癌症免疫学计划 肿瘤微环境和癌症免疫学(TMCI)计划的首要目标是定义如何 癌细胞、免疫细胞、间质成分和血管系统之间的动态相互作用调节 恶性肿瘤的生长和扩散，并在这样做的过程中，确定治疗方法来调节 微环境与肿瘤生长。该方案由13名教员(1名新聘人员)和5名助教组成 成员，并整合其专业知识包括细胞迁移/入侵、分子结构、细胞 信号、细胞新陈代谢和血管生成，其工作包括靶向治疗 先天免疫细胞和获得性免疫细胞以及微生物群对肿瘤和免疫细胞导向的影响 癌症疗法。这种互补的专业知识围绕三个相互作用的主题组织：(1)激活 侵袭和转移；(2)避免免疫破坏；(3)肿瘤促进炎症。这些 主题包含许多分子过程，这些过程协调微环境的形成， 促进肿瘤的生长和转移。成员在多个层次上进行互动，包括每月 教职员工会议、计划主导的研讨会(上个资助期有48个)、围绕新的 协作机会(例如，人类微生物组与癌症的接口)和协作 资助金。计划资金强劲，目前年度赠款资金总额为440万美元(直接成本)(260万美元来自 NCI，58%)。成员目前领导28项赠款，其中包括15项R01(9项来自NCI)，并领导或参与3项 P01(两个来自NCI)，以及多个其他赠款。在过去的资助期内，会员参与了34项 (32%)协作性赠款。我们的生产力在上一次资助的224份与癌症相关的出版物中得到了反映 期间，其中31%是协作性的(19%是方案内的，12%是方案间的)。2018年，我们发表了42篇 癌症相关出版物，其中21%是方案内出版物，5%是方案间出版物。TMCI成员拥有 开创性的新方法来询问肿瘤细胞和内部其他细胞类型的基本属性 肿瘤，并正在开发免疫细胞和肿瘤靶向治疗。会员们正在参与 通过肿瘤学疾病小组、C3癌症中心理事会和圣地亚哥的翻译倡议 精确免疫治疗中心，该中心支持与当地肿瘤学家的合作，以使 协作性赠款申请。在认识到免疫系统在抗击癌症中的作用时，一个关键 该计划的目标是建立和进一步加强癌症免疫学的专业知识，雇用至少两名 增加教员，包括一名具有疫苗学专业知识的教师。关键的科学目标是扩大对 感染模型为利用免疫系统进行免疫治疗和癌症疫苗的研究提供信息 以及整合单细胞转录组学、蛋白质组学、表观遗传学以及代谢图谱和成像 肿瘤中的癌细胞、免疫细胞和基质细胞，以获得对肿瘤生长调节的新见解 导致肿瘤耐药和免疫逃避的结果和细胞过程。

ABSTRACT – TUMOR MICROENVIRONMENT AND CANCER IMMUNOLOGY PROGRAM The overarching goal of the Tumor Microenvironment and Cancer Immunology (TMCI) Program is to define how the dynamic interplay among cancer cells, immune cells, stromal components, and vasculature regulates the growth and dissemination of malignancies, and in so doing, identify therapeutic approaches to modulate the microenvironment and tumor growth. The Program consists of 13 faculty (one a new recruit) and five adjunct members, and integrates members whose expertise includes cell migration/invasion, molecular structures, cell signaling, cell metabolism, and angiogenesis, with members whose work encompasses therapeutic targeting of innate and adaptive immune cells, and the influence of the microbiome on tumor- and immune cell-directed cancer therapies. This complementary expertise is organized around three interacting themes: (1) Activating Invasion and Metastasis; (2) Avoiding Immune Destruction, and (3) Tumor Promoting Inflammation. These themes encompass many of the molecular processes that coordinate the formation of the microenvironment that enables progressive tumor growth and metastasis. Members interact on several of levels, including monthly faculty meetings, program-led seminars (48 in the last funding period), strategic meetings organized around new collaborative opportunities (for example, the interface of the human microbiome and cancer), and collaborative grants. Program funding is strong, with current total annual grant funding of $4.4M (direct costs) ($2.6M from NCI, 58%). Members currently lead 28 grants including 15 R01s (nine from NCI), and lead or participate in three P01s (two from NCI), and multiple other grants. Over the last funding period, members have participated in 34 (32%) collaborative grants. Our productivity is reflected in 224 cancer-relevant publications in the last funding period, of which 31% were collaborative (19% intra- and 12% inter-programmatic). In 2018, we published 42 cancer-relevant publications, of which 21% were intra- and 5% inter-programmatic. TMCI members have pioneered novel approaches to interrogate the fundamental properties of tumor cells and other cell types within tumors, and are developing immune cell- and tumor-targeted therapies. Members are participating in translational initiatives through the Oncology Disease Teams, C3 Cancer Center Council, and the San Diego Center for Precision Immunotherapy, which support collaborations with local oncologists to enable large collaborative grants applications. In recognition of the role of the immune system in combatting cancer, a key goal of the Program is to build and further strengthen expertise in cancer immunology by hiring at least two additional faculty, including one with expertise in vaccinology. Key scientific goals are to extend the use of infection models to inform studies to harness the immune system for immunotherapy and cancer vaccines as well as to integrate single-cell transcriptomics, proteomics, epigenetics, and metabolic profiling and imaging of cancer cells, immune cells, and stromal cells in tumors to achieve new insights into the regulation of tumor growth outcomes and cellular processes that lead to drug resistance and immune evasion by tumors.