Inge Tinhofer

Presenation
Head and neck squamous cell carcinoma (HNSCC) remains a highly aggressive malignancy with dismal outcomes in advanced stages, despite progress in surgery, radiotherapy, and systemic treatments. Increasing evidence from correlative studies in clinical cohorts and molecular and functional studies in preclinical models underscores the pivotal role of the tumor microenvironment (TME) in shaping disease progression and therapeutic response. Notably, HNSCCs associated with human papillomavirus (HPV) display distinct molecular and immune profiles compared to HPV-negative tumors, offering a unique window for personalized therapeutic strategies.

The TME in HNSCC is marked by extensive heterogeneity and immunosuppressive features, which not only drive tumor growth and resistance mechanisms but also significantly impact prognosis. Also, the tumor extracellular matrix is markedly stiffer than normal tissue due to collagen deposition and desmoplastic remodeling – biomechanical changes that have been implicated in tumor progression and treatment resistance. ECM stiffness modulates key cellular processes including integrin signaling, drug diffusion, and oxygen availability – all of which are relevant to radiation and chemotherapy responses. Despite growing evidence of the role of matrix mechanics in therapy resistance, these factors remain understudied in HNSCC due to a lack of suitable experimental models.

This presentation will explore the complex interactions within the TME that influence critical processes such as epithelial-mesenchymal transition (EMT), tumor cell survival, immune evasion, and DNA damage repair. I will also examine how these dynamics contribute to the emergence of more aggressive phenotypes and treatment resistance. Finally, the lecture will discuss current and emerging therapeutic approaches targeting the TME, highlighting how a deeper understanding of the TME in both HPV+ and HPV− HNSCC is paving the way for more effective and individualized treatment paradigms.

Bio
Prof. Tinhofer-Keilholz did her studies of biology at the University of Innsbruck, Austria. After graduation in 1996 she worked as Post-Doc at the Department of Hematology and Oncology with a strong translational research focus in leukemia and multiple myeloma. In April 2006 she habilitated for Immunology / Tumor Immunology at the University Hospital Salzburg where she was working as group leader and chair of the Laboratory for Immunological and Molecular Cancer Research. Since 2008 Prof. Tinhofer-Keilholz heads the translational research laboratory of the Department of Radiooncology and Radiotherapy at the Charité University Hospital Berlin. In 2017, she was appointed as Associate Professor at the Charite.
The research interest of Inge Tinhofer-Keilholz focuses mainly on the elucidation of the molecular mechanisms which render HNSCC cells resistant to radiotherapy, chemotherapy and targeted treatment. By in-depth characterization of preclinical models and patient material from clinical trials she is aiming at the development of biomarkers for improved patient stratification and personalized treatment.
Inge Tinhofer-Keilholz has published 140 scientific papers. From 2010-2022, she coordinated the research activities of the Charité Comprehensive Cancer Center Working Group Head and Neck Cancer. From 2015 to 2022, she was Translational Research Representative from the EORTC HNC Group. Since 2020 she is member of the ESMO Faculty (HNC Group). She serves as reviewer for Nature Cancer, Scientific Reports, Lancet Oncology, Oncotarget, Clinical Cancer Research, Annals of Surgical Oncology, Annals of Oncology, Cancer, European Journal of Cancer, Clinical Cancer Research, BMC Cancer, International Journal of Cancer and Frontiers in Oncology.