Exosomes are virus-sized vesicles that are produced by every cell and represent an effective means of intercellular communication. They contain a great deal of information from the mother cell in the form of RNA, DNA and proteins and can pass this on to the recipient cell in concentrated form. Our research group has shown that head and neck tumour cells increasingly produce exosomes and that these exosomes pass on a wide range of information to immune cells, thereby inhibiting or activating them.

We are investigating the interaction of exosomes with immune cells and which mechanisms are responsible for this. These range from surface contacts via checkpoint molecules, enzymatic production of adenosine from ATP to epithelial-mesenchymal transition.

Furthermore, we were able to show that exosomes transport checkpoint molecules to their surface. These correlate with clinical parameters of head and neck carcinoma patients and can influence the functions of effector T cells (Theodoraki et al. Clinical Cancer Research 2017, Clinical & Experimental Immunology 2018). Our research group is evaluating the potential of exosomes as "liquid biomarkers".

Photodynamic therapy (PDT) is a treatment option for head and neck cancer patients in the palliative situation. With the help of light sensitisers, which accumulate in the tumour tissue, energy is transported into the tumour and elimination of the tumour cells is induced. This therapy causes a short-term destruction of the tumour cells with a local inflammatory reaction and long-term activation of the immune system. Understanding the exact mechanisms responsible for the anti-tumour immune response can contribute to further improvements in photodynamic therapy (Theodoraki et al. Photodiagnosis Photodyn Ther. 2017, Anticancer Research 2016)

Research is also being conducted into the extent to which different therapy methods influence the Kargo and the activity of exosomes and whether they can provide indications of a response to therapy.

In order to specifically alter the tumour microenvironment, we have established a special ex vivo tumour model in which patients' tumours can be treated with immunoactive substances, such as TLR3 ligands or checkpoint inhibitors. The aim is to enhance an anti-tumour immune response by

a.) promoting effector T cell migration

b.) Inhibition of regulatory T cell migration

This is achieved by modulating the chemokine and cytokine constellation as well as the exosomes and investigating the molecular biological signalling pathways. Macrophages play a very special role here due to their high production of immunosuppressive molecules such as COX2, CXCL12 and CCL22.

- cand. rer. nat. Linda Hofmann

Topic: The relevance of tumour-associated exosomes as "liquid biopsies" in head and neck carcinomas

- cand. med. Inga Beccard

Topic: Immunosuppressive effects of tumour derived exosomes (TEX) from head and neck carcinoma patients on T cells (cooperation project with Prof. Dr Schuler)

Scholarship holder of the Experimental Medicine doctoral programme at the University of Ulm

- cand. med. Jan Schröder

Topic: Influence of exosomes on regulatory B lymphocytes in patients with head and neck carcinomas (cooperation project with Prof Dr Schuler)

Scholarship holder of the Experimental Medicine doctoral programme at the University of Ulm

- cand. med. Marie Waizenegger

Topic: Influence of circulating exosomes from head and neck carcinoma patients on epithelial-mesenchymal transition

Scholarship holder of the Experimental Medicine doctoral programme at the University of Ulm

Charlotte Kötting -cand. med.

Topic: Influence of curcumin on the immunoinhibitory profile of the tumour microenvironment in head and neck carcinomas

-Valentin Medyany, MD

Topic: Immunoinhibitory effects of exosomes from the saliva of head and neck carcinoma patients

Scholarship holder of the Experimental Medicine doctoral programme at the University of Ulm

- cand. med. Florian von Strachwitz

Topic: Establishment of direct tumour-specific exosome staining for the evaluation of tumour burden in head and neck carcinoma patients

- cand. dent. Janina Matheis

Topic: Evaluation of tumour markers on exosomes of head and neck cancer patients and corresponding tumour samples

• DFG research fellowship (2016-2018)
• Young Scientist Award of the Württemberg Cancer Prize 2018, Dres. Bayer Foundation Tübingen
• Awards from the European Association of Cancer Research 2018, Society for Immunotherapy of Cancer 2016, American Association of Immunologists 2017 and 2018
• Alexander Karl Prize 2018 from the Head and Neck Tumour Research Foundation
• Clinical Science Award 2018, German Society for Immune and Targeted Therapy e.V.
• DFG project funding 2019-2021
• Research funding from the Walter Schulz Foundation
• Research funding from the Brigitte and Dr Konstanze Wegener Foundation 2020
• Research funding by the German Cancer Aid 2021-2024

David L. Bartlett, MD:Department of Surgical Oncology, University of Pittsburgh

Soldano Ferrone, MD: Department of Surgery, Harvard Medical School, Boston

Nick Giannoukakis, MD, PhD:Department of Pathology, University of Pittsburgh

Edwin K. Jackson, PhD:Pharmacology and Chemical Biology, University of Pittsburgh

Monika Pietrowska, PhD: Institute of Oncology, Gliwice

Prof Dr Ramin Lotfi, University Hospital Ulm, Transfusion Medicine / DRK

Saumendra Sarkar, PhD: Department of Microbiology and Molecular Genetics, University of Pittsburgh

Prof Dr Walther Vogel, University Hospital Ulm, Genetics

Theresa L. Whiteside, PhD, MD: Department of Pathology, University of Pittsburgh