The influence of neutrophil granulocytes on tumorigenesis and tumortherapy

中性粒细胞对肿瘤发生及肿瘤治疗的影响

• 批准号: 204014845
• 负责人: Dr. Christian Idel
• 金额: --
• 依托单位: Department of Pathology
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/204014845?language=en
• 关键词: influence; neutrophil; granulocytes; tumorigenesis; tumortherapy

Polymorphonuclear (neutrophilic) granulocytes (PMN) are the largest subpopulationof leukocytes. In the past, PMN were mainly thought of as the first line of defense by immune cells in the inflammation site. The only role they had in that picture was phagocytosis, killing and becoming necrotic or apoptotic. But recently, there has been a major change in the understanding of the role of PMN. These cells not only play a major role at the beginning of inflammation but also in resolving, i.e., ending of the inflammation. At the beginning of the inflammation, a major fraction of PMN become necrotic at the inflammation site. This promotes the proinflammatory functions of different immune cells including PMN. During the later stages of inflammation, a larger fraction of PMN becomes apoptotic and smaller fraction necrotic. This way the antiinflammatory functions of different immune cells are promoted and the proinflammatory functions are reduced or terminated.Little is known about how cancer cells can escape the immune system. PMN are the biggest subpopulation of leukocytes in periphral blood, and PMN are found regularly in solid tumors. But we know little that much about the interaction and influence of PMN on cancer cells and vice versa. The same holds true with regards to the relationship between PMN and other types of immune cells in solid cancer tumors, such as macrophages, NK-cells or dendritic cells. In my project about the PMN role in cancer, I plan to study cytokine production, phagocytosis, oxidative burst, cell surface markers, life spans and the different pathways of cell death in these different cell types in solid tumors. Of special interest will be determining the mechanisms whereby the tumor avoids an attack by the immune system and how to induce a profound immune reaction against a tumor.

多形粒细胞（PMN）是白细胞中最大的亚群。过去，PMN主要被认为是炎症部位免疫细胞的第一道防线。它们在这幅图中的唯一作用是吞噬、杀死和坏死或凋亡。但最近，对PMN作用的认识发生了重大变化。这些细胞不仅在炎症开始时起主要作用，而且在消退中也起主要作用，即，结束炎症。在炎症开始时，大部分PMN在炎症部位坏死。这促进了包括PMN在内的不同免疫细胞的促炎功能。在炎症的后期阶段，较大比例的PMN变为凋亡，较小比例的PMN变为坏死。通过这种方式，不同免疫细胞的免疫功能被促进，促炎功能被减少或终止。关于癌细胞如何逃脱免疫系统的知之甚少。 中性粒细胞是外周血中最大的白细胞亚群，在实体瘤中有规律的发现。 但我们对PMN与癌细胞的相互作用和影响知之甚少，反之亦然。 这同样适用于实体癌肿瘤中PMN与其他类型的免疫细胞（如巨噬细胞、NK细胞或树突状细胞）之间的关系。 在我关于PMN在癌症中的作用的项目中，我计划研究细胞因子的产生，吞噬作用，氧化爆发，细胞表面标志物，寿命以及实体瘤中这些不同细胞类型的细胞死亡的不同途径。特别感兴趣的是确定肿瘤避免免疫系统攻击的机制以及如何诱导针对肿瘤的深刻免疫反应。