Radiotherapy-induced mechanisms of neutrophil-driven immunological control of Head and Neck Squamous Cells Carcinoma

• Applicants: Privatdozent Dr.-Ing. Benjamin Frey; Privatdozent Dr. Luis Munoz
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 558957753

As radiotherapy (RT) is integral part of multimodal treatment of head and neck squamous cell carcinoma (HNSCC) and since previous work suggests a not yet fully understood modulation of neutrophils functions by RT, our key objectives are to reveal both, mechanisms of neutrophil-driven cancer progression and immune evasion as well as mechanisms of potential beneficial anti-tumor effects during RT of HNSCC. We hypothesize that RT not only acts through a direct damage of tumor cells in HNSCC, but also through the activation of specific pathways in epithelial cells that consecutively affect phenotype and effector functions of neutrophils and subsequently the effector functions of T cells. For this, comprehensive analyses at the single cell level integrated with histological information from a murine tumor model are necessary to characterize the role of tumor infiltrating neutrophils induced by RT. The proposal has four key aims, first to gain knowledge about the impact of RT per se and of irradiated HNSCC cells on migration and phenotype of neutrophils. Second, to evaluate the impact of RT on organs of the head and neck region that might trigger the activation of neutrophils. Third, to characterize the mechanisms mediated by neutrophils that modify orthotopic tumor growth in mice exposed to RT. Fourth, to compare the preclinical data collected with neutrophil effector functions and outcome of patients with HNSCC treated with surgery and RT.

• DFG Programme: Research Grants