Regulation of Antitumor Immunity by DC Subsets

该K01指导职业发展奖项的广泛目标是获得肿瘤免疫学和树突状细胞（DC）生物学领域的深入研究培训和经验，最终目标是成为开发新型抗肿瘤治疗方式的独立研究者。本研究方案基于DC亚群在抗肿瘤免疫应答的启动和调控中起着非常重要的作用，其功能会受到肿瘤微环境和肿瘤源性因素的影响。为了验证这一假设，我们将研究两个具体目标，即(1)髓系和淋巴系DC亚群的功能分析和比较；(2)肿瘤源性因子对DC不同亚群抗原递呈功能的影响。本提案的重要性在于，由于难以获得纯DC子集，因此很少对DC子集进行研究，并且可以从hFlex基因处理的小鼠中分离出高纯度的DC子集，这是本实验室新开发的方法。这个候选人非常适合做这项研究。他在医学、分子生物学和基因传递方面受过良好的训练，在他的17篇同行评审的出版物和3篇提交的手稿中都有记载。该候选人致力于利用基因传递和分子生物学的知识和技术研究DC生物学，开发新的癌症治疗方式。这两个目标涉及现代免疫学和生物学的所有基本知识和技术。结合候选人在分子生物学方面的强大背景，以及他将通过拟议的研究获得的肿瘤免疫学和DC生物学方面的培训。通过利用分子生物学、肿瘤免疫学和DC生物学的知识和技术，他将在开发新的抗肿瘤方法领域成为一名独立研究者。这个奖项的候选人所选择的环境是杰出的。导师Louis D. Falo Jr.博士在肿瘤免疫学和DC生物学领域有着良好的声誉和资金支持。匹兹堡大学癌症研究所（UPCI）以其在肿瘤免疫学和DC应用方面的实力而闻名。罗纳德·赫伯曼，特蕾莎·怀特塞德和奥利维拉·芬恩。UPCI在直流生物学和应用方面拥有最大的研究团队。院系和机构资源丰富，学术环境优越，在癌症生物学、肿瘤免疫学和DC生物学领域有三个成熟的系列研讨会和一个期刊俱乐部。此外，其他癌症相关的研讨会也可以从医学院的其他部门获得。研究所承诺通过提供所有资源来全力支持候选人。候选人、研究计划和环境共同为该奖项提供了强有力的申请。

The broad objective of this K01 mentored career development award is to obtain in depth research training and experience in the field of tumor immunology and dendritic cell (DC) biology, with the ultimate goal of becoming an independent investigator for developing novel anti-tumor treatment modalities. The research proposal is based on the hypothesis that DC subsets play a very important role in the initiation and regulation of anti-tumor immune response and their function will be affected by the tumor microenvironment and tumor-derived factors. For testing this hypothesis, we will study two specific aims, i.e., (1) Functional analysis and comparison of myeloid and lymphoid DC subsets; (2) Influence of the tumor derived factors on the antigen presentation function of different subsets of DC. The importance of this proposal lies in the fact that DC subsets are scarcely studied due to the difficulty of obtaining pure DC subsets and on the ground that highly pure DC subsets can be isolated from hFlex gene treated mice, which is a newly developed approach in this lab. The candidate is highly suited to perform the research. Dr. He is well trained in medicine, molecular biology, and gene delivery as documented in his 17 peer-reviewed publications and three submitted manuscripts. The candidate is committed to using the knowledge and techniques of gene delivery and molecular biology to study the DC biology and develop novel cancer treatment modalities. The two aims involve all the basic knowledge and techniques of modern immunology and biology. Incorporating the strong background in molecular biology the candidate already has with the training in tumor immunology and DC biology as he will receive through the proposed research., he will be positioned very well in the path towards an independent investigator in the field of developing new anti-tumor approaches by harnessing the knowledge and techniques of molecular biology, tumor immunology and DC biology. The environment the candidate chosen for this award is outstanding. The mentor, Dr. Louis D. Falo Jr., is well established and well funded in the field of tumor immunology and DC biology. The University of Pittsburgh Cancer Institute (UPCI) is well known for its strength in tumor immunology and DC application under the leadership of Drs. Ronald Herberman, Theresa Whiteside and Olivera Finn. The UPCI has the largest research team on DC biology and application. The departmental and institutional resources are excellent and the intellectual environment is superb as there are three well-established seminar series in the area of cancer biology, tumor immunology and DC biology and one journal club. In addition, other cancer related seminars are also available from other departments in the school of medicine. The institute is committed to fully support the candidate by providing access to all of the resources. Together, the candidate, research proposal, and the environment provide a strong application for this award.