The Tisch Cancer Institute - Cancer Center Support Grant

 描述（由申请人提供）：癌症进展的特征是免疫系统在多个水平上逐渐失调，被认为直接导致肿瘤生长不受抑制。癌症免疫学（CI）研究计划的中心主题是确定抑制有效抗肿瘤免疫的潜在机制，这些机制可以指导新型和有效免疫疗法的开发。树突状细胞（Dendritic cells，DCs）是一种强有力的抗原提呈细胞，可启动抗肿瘤免疫应答，并由CD 4+辅助细胞和细胞毒性T细胞介导。免疫学家历来专注于表征肿瘤浸润T细胞（TILs）在抑制肿瘤生长中的作用，但有新的证据表明，先天免疫细胞，如DC和巨噬细胞，受到肿瘤微环境（TME）的强烈影响，是肿瘤进展的主要贡献者。 CI研究计划有三个主要科学目标。它们将：1）表征肿瘤微环境中DC和巨噬细胞免疫失调的潜在机制; 2）开发临床前模型，以逆转先天免疫功能障碍并恢复肿瘤相关抗原的免疫原性; 3）将临床前发现转化为癌症免疫治疗试验。 CI计划有21名成员，他们代表10个部门和3个研究所（Tisch癌症研究所，免疫学研究所，伊坎基因组学和多尺度生物学研究所）。截至2014年7月1日，计划成员获得了NCI和其他同行评审的癌症相关直接支持的4，016，010美元。CI计划的成员越来越成功地在高影响力期刊上发表他们的研究。自2011年以来，传播和信息项目成员发表了163份报告，其中14.7%是项目内报告，23.9%是项目间报告。

 DESCRIPTION (provided by applicant): Cancer progression is characterized by gradual dysregulation of the immune system at multiple levels that is considered to directly contribute to unchecked tumor growth. The central theme of the Cancer Immunology (CI) Research Program is to identify mechanisms underlying the suppression of effective anti-tumor immunity that could instruct the development of novel and impactful immunotherapies. Dendritic cells (DCs), potent antigen presenting cells, initiate anti-tumor immune responses, which are subsequently mediated by CD4+ helper cells and cytotoxic T cells. Immunologists have historically focused on characterizing the role of tumor infiltrating T cells (TILs) in restraining tumor growth, but thereis emerging evidence that innate immune cells, such as DC and macrophages, are strongly affected by the tumor micro-environment (TME) and major contributors to tumor progression. The CI Research Program has three main scientific objectives. They are to: 1) Characterize mechanisms underlying DC and macrophage immune dysregulation in the tumor micro-environment; 2) Develop preclinical models to reverse innate immune dysfunction and restore immunogenicity to tumor associated antigens, and 3) Translate preclinical discoveries into cancer immunotherapy trials. The CI program has 21 members, and they represent 10 departments and 3 institutes (The Tisch Cancer Institute, Immunology Institute, Icahn Institute for Genomics and Multiscale Biology). As of July 1, 2014, program members were awarded $4,016,010 in NCI and other peer reviewed cancer-related direct support. Members of the CI Program have been increasingly successful in publishing their research in high impact journals. Since 2011, CI program members published 163 reports, of which 14.7% were intra-programmatic and 23.9% inter-programmatic.