Immunological Changes under Standard of Care Therapy of Head and Neck Squamous Cell Carcinoma
Hematology, Oncology
Final Report Abstract
In the funded project, I sought to investigate chemoradiotherapy (CRT) induced changes to immune functions locally and peripheral. Combination regimen of chemoradiotherapy and immunotherapy for head and neck carcinoma are emerging, but, so far, trials have been negative. To improve these concepts it is crucial to understand the influence of CRT more detailed. Further, it is relevant to identify patients which will respond poorly to CRT beforehand. One of the projects in the funded period was focused on the tumour microenvironment (TME). We analysed patient samples before and after CRT on a transcriptomic level and could identify changes in T cell populations which were associated to response. Protective tissue resident memory cells, for example, were decreased by CRT in patients without complete response, whereas they remained stable in patients with complete response. To evaluate cell interactions in the TME more closely, an imaging mass cytometry panel was designed and first markers established. This technique enables us to identify a broad spectrum of immune cell subtypes in a spatial resolution. Results are expected within the coming year. To analyse changes to the immune system globally, antigen-specific T cell have to be identified in the peripheral blood. As these cells are rare, it is needed to define or identify the antigen beforehand. To screen patients for the antigen of interest, MAGED4B, I established an ELISA assay and screened patients and healthy controls. In parallel, a flow cytometry panel for the analysis of cytotoxic CD4+ T cells was composed as these cells have been shown to be highly antigen-specific in cancer patients. Further research on this topic is ongoing. While analysing immune cell changes in the TME and peripherally, it became clear that a mere snapshot of the cell states at a certain time point might not suffice to evaluate immune competence precisely. Therefore, I designed several work programs, both in vitro and in vivo, to examine the functional capacity of individuals to respond to neo-antigens under several conditions. The projects are currently prepared and will start within the next two months.
Publications
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Changes in Gene Expression Patterns in the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma Under Chemoradiotherapy Depend on Response. Frontiers in Oncology, 12.
Doescher, Johannes; von Witzleben, Adrian; Boukas, Konstantinos; Weissinger, Stephanie E.; Thomas, Gareth J.; Laban, Simon; Thomas, Jaya; Hoffmann, Thomas K. & Ottensmeier, Christian H.
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Patterns of Tumor Infiltrating Lymphocytes in Adenoid Cystic Carcinoma of the Head and Neck. Cancers, 14(6), 1383.
Doescher, Johannes; Meyer, Moritz; Arolt, Christoph; Quaas, Alexander; Klußmann, Jens Peter; Wolber, Philipp; Bankfalvi, Agnes; Schildhaus, Hans-Ulrich; Bastian, Tobias; Lang, Stephan; Laban, Simon; Schuler, Patrick J.; Brunner, Cornelia; Hoffmann, Thomas K. & Weissinger, Stephanie E.
