The influence of neutrophil granulocytes on tumorigenesis and tumortherapy

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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.