Despite all research efforts, the majority of advanced tumours in the head and neck region successfully evade treatment. As a consequence, patients suffer from tumours that grow recurrently or metastasise and significantly shorten their survival time.

In addition to the downregulation of immunogenic surface molecules and the expression of immunosuppressive messenger substances, regulatory immune cells play a particularly important role in immune escape. Both progressive tumour growth and the respective oncological therapy can permanently alter the immune system of tumour patients. As it has become clear to us in recent years how much the immune system can influence tumour growth, this interaction between tumour cells and regulatory immune cells is the focus of the working group.

Adenosine-producing B cells with immunosuppressive properties can regularly be detected in the blood and tumour tissue of tumour patients. Bruton's tyrosine kinase (BTK) is a central element of the intracellular signalling chain in these regulatory B cells. The relationships between adenosine production, blockade of BTK and B cell function are being investigated in detail. Publication: Jeske SS et al, Cancer Immunology Immunotherapy. 2020 Jul;69(7):1205-1216.

Adenoid cystic carcinoma of the salivary glands is a malignant tumour that differs fundamentally from the frequently occurring squamous cell carcinoma due to its slow growth and atypical haematogenous metastasis pattern. The investigation of the immune infiltrate can help to improve the treatment of this rare tumour entity and open up the possibility of immunotherapeutic approaches. Publication: Jeske S et al, Eur Arch ORL. 2019 May;276(5):1465-1473.

Project management: cand. med. Lisa Puntigam, M.Sc.

With the successful introduction of checkpoint inhibitors, immunotherapy is playing an increasingly important role in the treatment of tumour patients. The mutual interactions between checkpoint inhibition and standard therapy, such as radiochemotherapy, are still unclear. As part of her Master's thesis in molecular medicine, Ms Puntigam investigated the expression of checkpoint receptors on various immune cells. Ms Puntigam has received travel grants from the German ENT Society and the Hertha Nathorff Programme of the University of Ulm and is currently continuing the project as a research assistant.

Project management: Dr Johannes Döscher

1. the treatment options for patients with advanced head and neck cancer are often limited. A biopanel is used to detect various proteins on the tumour cells, which can then enable palliative antibody therapy. The expression pattern of various tumour entities and the clinical course of the treated patients are being analysed as part of the translational research project in close cooperation with colleagues from the Department of Pathology.

2. the expression of inflammatory cytokines by human T cells is an essential component of the immune response in tumour patients. Modern flow cytometry methods allow the detection of multiple cytokines in individual T cells. This allows conclusions to be drawn about the polyfunctionality of the cells. This study investigates how this function of T cells changes in patients undergoing radiochemotherapy. Publication: Döscher et al, Radiother. Oncol., 2018.

3 Another project is investigating the changes in immune checkpoints under primary radiochemotherapy. This should make it possible to define the best form of immunotherapy and the optimal timing in combination with classic radiochemotherapy.

Project management: Dr Marlene Wigand

The group of tumour patients of advanced age is constantly growing due to demographic developments and improved medical care. New immunotherapeutic approaches may be of particular interest to this group of patients due to their favourable side-effect profile. In order to design effective therapy, the changes in the immune system in old age must be understood. This translational work examines immune cells in the blood and tumour tissue of patients of different age groups. Publications: Jeske SS et al. Immunity & Ageing. 2020 Feb 12;17:3 & Wigand et al, ENT. 2020 Mar;68(3):177-183

Mr Ju Xin started his experimental doctoral thesis in our oncological research laboratory in October 2017. He completed his specialist training as a thoracic surgeon at our partner university in Nanjing, China, and is joining our laboratory team as part of the international cooperation programme. The focus of his research work is on immunoregulatory cells in patients with head and neck tumours. In particular, he is investigating the influence of the tumour microenvironment on the checkpoint expression of immune cells.

Cooperation project with PD Dr Marie-Nicole Theodoraki

Photodynamic therapy is a treatment option for patients with head and neck cancer in a palliative situation. With the help of light sensitizers, which accumulate in the tumour tissue, energy is transported into the tumour and elimination of the tumour cells is induced. Despite the localised nature of this therapy, multiple systemic changes in the patient's immune system can be detected. Understanding these can contribute to a further improvement of photodynamic therapy. Publication: Theodoraki et al, Photodiagnosis Photodyn Ther., 2017.

Cooperation project with PD Dr Marie-Nicole Theodoraki.

Regulatory B cells are an important component of the tumour microenvironment in head and neck cancer, and their manipulation can potentially improve the treatment of tumour patients. In addition to the classic intercellular signalling pathways such as cell-cell contact or cytokine expression, it has now been shown that cells can also communicate with each other by means of actively secreted exosomes. These exosomes possess many properties of the cell of origin and can influence the function of other immune cells. This study investigates how exosomes from different cells of origin influence the function of regulatory B cells. Publications: Schroeder et al, Cancers. 2020 Jul 29;12(8):E2110. & Beccard et al, Cancers. 2020 Jul 21;12(7):E1997.