Imaging CD8 Immunity in Cancer

癌症患者可能存在大量激活的肿瘤特异性T细胞，这些T细胞可能表现出杀瘤作用 在体外具有活性，但在大多数情况下无法在体内根除肿瘤。了解失败的原因 抗肿瘤免疫反应的研究以及开发有效的治疗方法需要 淋巴组织和非淋巴组织中T细胞反应的体内机制的阐明。这个 对免疫反应的研究在很大程度上限于从淋巴组织中提取的细胞 分析了体外或体外重新刺激的情况。该项目的总体目标是验证和 使用非侵入性活体成像技术客观监测自发产生的肿瘤特异性 以及测量免疫治疗方式对这些反应的影响 在活体内。在第一个目标中，我们将研究肿瘤特异性CD4T细胞(Theiper和Treg)如何干扰 肿瘤特异性CD8T细胞向肿瘤的迁移。在第二个目标中，我们将使用新的多模式单元 可能用于人类监测体外激活的肿瘤特异性T细胞的示踪剂 荷瘤小鼠的过继转移免疫治疗。在第三个目标中，我们将确定交互 肿瘤引流淋巴结和肿瘤床中肿瘤特异性CDS T细胞的细胞毒活性。 破译肿瘤特异性的CD4Treg如何控制抗肿瘤免疫是非常重要的 反应，以及如何通过使用有效的免疫疗法来防止它们的干扰。该项目将 与Ntziachristos实验室(CMIR的生物光学和分子成像实验室)进一步密切互动 开发和验证荧光蛋白断层扫描，并与哈佛大学的几个免疫学小组合作 (Von Boehmer和Khazaie在DFCI，Mathis在Joslin)。这个项目的最终目标是了解如何 为了开发更有效的免疫治疗方法，在体内控制免疫耐受。

Cancer patients can harbor high numbers of activated tumor-specific T cells that may exhibit tumoricidal activity in vitro but in most cases fail to eradicate the tumor in vivo. Understanding the reasons for the failure of anti-tumor immune responses, as well as developing efficient therapeutic approaches, requires the elucidation of in vivo mechanisms behind T cell responses both in lymphoid and nonlymphoid tissues. The study of immune responses has been largely limited to cells retrieved from lymphoid tissues that are analyzed either ex vivo or upon in vitro restimulation. The overall goal of this Project is to validate and employ noninvasive intravital imaging techniques to objectively monitor spontaneously arising tumor-specific T cell responses as well as measure the impact that immunotherapeutic modalities have on these responses in vivo. In the first aim, we will study how tumor-specific CD4 T cells (Theiper and Treg) interfere with the migration of tumor-specific CD8 T cells to tumors. In the second aim, we will use novel multimodal cell trackers with potential use in humans for the monitoring of in vitro activated tumor-specific T cells following adoptive transfer immunotherapy in tumor-bearing mice. In the third aim, we will determine the interactive and cytotoxic activity of tumor-specific CDS T cells in tumor draining lymph nodes and in the tumor bed. There is a strong emphasis on deciphering how tumor-specific CD4 Treg control anti-tumor immune responses, and how their interference can be prevented by using efficient immunotherapies. The project will interact closely with the Ntziachristos lab (Lab for Biooptics and Molecular Imaging at CMIR) in further developing and validating fluorescent protein tomography, and with several immunology groups at Harvard (von Boehmer and Khazaie at DFCI, Mathis at Joslin). The ultimate goal of this project is to understand how immune tolerance is controlled in vivo in order to develop more effective immunotherapies.