How senescent alveolar macrophages contribute to lung tumor development in aging.

• Applicant: Dr. Katharina Glaser
• Subject Area: Immunology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 555061910

Lung cancer is the leading cause of cancer-related deaths worldwide. It is especially common among the elderly, 50% of all cases are diagnosed in patients older than 70 years. Thus, we want to study lung cancer development in the light of aging. Macrophages are a type of immune cell that is often found near developing tumors. They contribute to the growth of blood vessels into the tumor, inflammation, and the spread of cancer cells to other parts of the body. This way, they promote tumor growth and disease progression. Recently, researchers have found that in lung cancer specifically senescent macrophages accumulate. Senescence is a condition often observed in cells of old people and animals. Senescent cells stop dividing, accumulate damage, and change their morphology and functionality. How such “old” macrophages contribute to lung tumor development, is however unknown. To answer this question, I will use a genetic mouse model in which the lack of a specific protein (Lamin A/C) leads to premature senescence of lung macrophages, but not other cells in the tissue. I will use this model to characterize “old” tumor-associated macrophages and their interaction with tumor cells. I will also combine this model with other genetic modifications, that affect protein and DNA disposal processes within the cells. I will study tumor growth in those mice and examine the interactions between macrophages and tumor cells through various techniques. To test mechanistic hypotheses, I will conduct experiments using a system, in which tumor cells grow together with macrophages in cell culture dishes outside of an organism. My goal is to uncover the mechanism of how senescent macrophages contribute to lung tumor development. I aim to understand the specific aspects of cell aging in macrophages that drive their tumor-promoting effect. This research will provide insights into how potential future cancer treatments can be tailored specifically to the elderly.

• DFG Programme: WBP Fellowship
• International Connection: France
• Host: Nicolas Manel, Ph.D.