讲座题目：Dynamic regulating the immune responses by different areas of human tumors

主 讲 人：郑利民 教授

教育部“长江学者”特聘教授，国家杰出青年科学基金获得者

现任中山大学生命科学院副院长，附属肿瘤医院生物治疗中心主任

沙龙座谈：2013年6月27日（周四）14:30 伟德BETVlCTOR1946B栋308会议室

学术报告：2013年6月27日（周四）15:30 伟德BETVlCTOR1946B栋5楼报告厅

邀 请 人：周大旺 教授

讲座简介：

Human solid tumors have been dynamically coevolved with host immune system and can be anatomically classified into different areas, each with distinct compositions and functional properties. In contrast to the immunosuppressive intratumoral areas, the peritumoral stroma in most human tumors comprise a significant amount of leukocyte infiltrate which was long assumed to represent the host response to tumors. We found that tumors can alter the normal development of macrophages (Mφ) that is intended to trigger transient early activation of monocytes in the peritumoral region, which in turn induces formation of suppressive Mφ in cancer nests of human tumors. The activated monocytes in the peritumoral region attenuated T-cell response by expressing B7-H1, and were superior to the suppressive tumor Mφ in inducing Th17/Tc17 expansion, and thus repurpose the inflammatory response away from anti-tumor immunity and towards tissue remodeling and proangiogenic pathways. These tumor-activated monocytes could also promote NK cell dysfunction and deletion by inducing transient early activation and subsequent apoptosis of NK cells, a process which is partially mediated by CD48 on monocytes. Moreover, we found that, upon encountering autologous T cells, tumor Mφ produce IL-12 to activate T cells with high CD69 expression. These CD69+ T cells effectively promote IDO expression in Mφ, and thus create “tolerizing” conditions in tumors. Our results give important new insights into the collaborative action of infiltrating immune cells at distinct micro-milieu that is exercised to counteract effective anti-tumor immunity in human. Such an active induction of tolerance in tumors has an obvious negative impact on the effectiveness of clinical immunotherapeutic approaches, and thus should be considered for the rational design of effective immune-based anti-cancer therapies.