Signalling pathways of T-helper-1-cell-cytokine-induced senescence

• Applicant: Professor Dr. Thomas Wieder
• Subject Area: Dermatology
• Term: from 2014 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 260597731

Besides surgical excision, chemotherapy and radiation therapy, immunotherapy of tumours has emerged as a promising new anticancer regimen. In the meantime, researchers found new biological principles that do not exclusively aim to eradicate tumours by cellular destruction. Especially cellular senescence, i.e. the permanent growth arrest of tumour cells, and the senescence surveillance of tumours by the immune system were described as very efficient anticancer mechanisms. We could recently demonstrate that the senescence program is not only an oncogene-triggered intrinsic barrier to fight cancer growth but that it can also be induced by extrinsic factors, such as the inflammatory cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF). In the proposed project, we want to focus on the signalling pathways that ultimately lead to permanent cell cycle arrest after cytokine treatment. For this, we can use multiple mouse tumour models including different transgenic receptor- or signal transducer knock-out mice. The biological relevance of the described signal transduction pathways for senescence induction in human cells will be investigated using established cancer cell lines. The results will substantially broaden our knowledge about the molecules involved in the signalling cascades of cytokine-induced senescence.

• DFG Programme: Research Grants
• Participating Person: Dr. Heidi Braumüller