Tumor Microenvironment and Cancer Immunology

肿瘤微环境与肿瘤免疫学 肿瘤微环境和癌症免疫学（TMCI）计划的总体目标是定义如何 癌细胞、免疫细胞、基质成分和脉管系统之间的动态相互作用调节肿瘤细胞的增殖和分化。 生长和传播的恶性肿瘤，并在这样做，确定治疗方法，以调节 微环境与肿瘤生长该计划由13名教师（一名新员工）和5名兼职教师组成。 成员，并整合其专业知识包括细胞迁移/入侵，分子结构，细胞 信号传导，细胞代谢和血管生成，其工作包括治疗靶向的成员 先天性和适应性免疫细胞，以及微生物组对肿瘤和免疫细胞定向 癌症治疗这种互补的专门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）促进肿瘤炎症。这些 主题包括许多协调微环境形成的分子过程， 使肿瘤生长和转移进行性。成员在几个层面上互动，包括每月 教师会议，计划为主导的研讨会（48在上一个资助期），围绕新的战略会议组织 协作机会（例如，人类微生物组和癌症的界面），以及协作 赠款。计划资金雄厚，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个赠款，包括15个R 01（9个来自NCI），并领导或参与三个 P01（两个来自NCI）和多个其他赠款。在上一个供资期间，成员参加了34个 (32%）合作赠款。我们的生产力反映在224癌症相关的出版物在过去的资金 在这一期间，其中31%是协作性的（19%是方案内的，12%是方案间的）。2018年，我们发布了42个 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成员有 开创了新的方法来询问肿瘤细胞和其他细胞类型的基本特性， 肿瘤，并正在开发免疫细胞和肿瘤靶向疗法。成员们正在参加 通过肿瘤疾病团队，C3癌症中心理事会和圣地亚哥 精准免疫治疗中心，支持与当地肿瘤学家合作， 协作赠款申请。认识到免疫系统在对抗癌症中的作用， 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，通过雇用至少两个 额外的教师，包括一个在疫苗学的专业知识。关键的科学目标是扩大使用 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，代谢谱和成像， 肿瘤中的癌细胞、免疫细胞和基质细胞，以实现对肿瘤生长调节的新见解 结果和细胞过程导致肿瘤的耐药性和免疫逃避。

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.