Imaging CD8 Immunity in Cancer

癌症患者可以携带大量的活化的肿瘤特异性T细胞，其可以表现出杀肿瘤活性。 在体外的活性，但在大多数情况下不能根除体内肿瘤。了解失败的原因 的抗肿瘤免疫反应，以及开发有效的治疗方法，需要 阐明淋巴和非淋巴组织中T细胞应答背后的体内机制。的 免疫应答的研究主要限于从淋巴组织中提取的细胞， 在离体或体外再刺激时分析。本项目的总体目标是验证和 采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 T细胞应答以及测量免疫调节方式对这些应答的影响 in vivo.在第一个目标中，我们将研究肿瘤特异性CD4 T细胞（Theiper和Treg）如何干扰肿瘤细胞的增殖。 肿瘤特异性CD8 T细胞向肿瘤的迁移。在第二个目标中，我们将使用新的多模态单元 具有在人体中潜在用途的跟踪器，用于监测体外活化的肿瘤特异性T细胞， 在荷瘤小鼠中的过继转移免疫疗法。在第三个目标中，我们将确定交互式 和肿瘤引流淋巴结和肿瘤床中肿瘤特异性CD8 T细胞的细胞毒活性。 研究重点是阐明肿瘤特异性CD4 Treg如何控制抗肿瘤免疫， 反应，以及如何通过使用有效的免疫疗法来预防它们的干扰。该项目将 与Ntziachrixin实验室（CMIR生物光学和分子成像实验室）密切合作， 开发和验证荧光蛋白断层扫描，并与哈佛的几个免疫学小组合作 (von DFCI的Boehmer和Khazaie，Joslin的马西斯）。这个项目的最终目标是了解如何 为了开发更有效的免疫疗法，在体内控制免疫耐受性。

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.