Project Details
Projekt
The influence of B cells on the therapeutic success of immunotherapy in patients with head and neck cancer
Subject Area
Otolaryngology, Phoniatrics and Audiology
Term
since 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 504016957
The role of tumor-infiltrating B cells in solid tumors has long been underestimated. Only in the last few years has it become clear that the presence of B cells is often associated with a good prognosis in a variety of solid cancers such as head and neck cancer (HNC). On the other hand, B cells are also assigned a tumor-promoting role, which is supported by several murine tumor models. For further investigations it is therefore necessary to further subdivide the B-cell population into immunocompetent effector B-cells and immunosuppressive regulatory B-cells.The possibilities of immunotherapy with checkpoint inhibitors (CPI), such as PD1 antibodies, have also led to an increase in survival in patients with KHT. Since patients with tumors who do not express the PD-L1 ligand, also benefit from this therapy, the exact mechanism of action of the PD-1 antibodies has not yet been clarified. Likewise, there are no reliable prognostic markers for this therapy.In the context of the present application, we are investigating how different B-cell populations can influence therapy with CPI. The first section examines how CPI can strengthen the immune system and in particular B-cell function in vitro. This is done using blood and tumor samples from patients with HNC or from healthy control donors. Mass spectrometry, UMAP flow cytometry and experiments with tumor organoids are used here.The second section focuses on the influence of CPI on the immune system in an established, orthotopic murine tumor model. In this model, CPI are combined with other antibodies (anti-CD20, anti-CD73) or B-cell-specific proteins are deleted by knockout methods.The third section examines how the function of B cells can be modified with the help of tumor-derived exosomes. These studies are carried out both in vivo and in vitro. The exosomes are isolated using mini-size exclusion chromatography and visualized by nanoparticle tracking.The fourth section correlates the clinical data of our tumor patients treated with CPI with the occurrence of B-cell populations and tertiary lymphoid structures in the tumor. Existing tumor microarrays allow the investigation of a large number of tumor samples. Serum samples from patients are examined for antigen patterns using multiplex serology.The aim of the application is to improve oncological therapy by manipulating B cells in the tumor microenvironment of patients with HNC. These results can be transferred to other types of tumors in the further course. The areas of activity of the two applicants, on the one hand in the clinic and on the other hand in the research laboratory, are complementary and thus promote the rapid and successful implementation of the suggested experiments.
DFG Programme
Research Grants
