Dendritic cells act as the gatekeepers between the innate and adaptive immune system. The primary function of these cells is to maintain tolerance to harmless antigens and molecules of self under immunological steady-state conditions, and trigger immunity in the presence of danger signals. Their outstanding ability to present antigen and selectively respond to various pathogens and environmental factors, with a subsequent quality control and fine-tuning of the cellular communication, clearly demonstrate their deterministic role in the adaptive immunity.
Several unique DC populations have been described in various human organs and improvements in single-cell analysis technologies now make it possible to obtain a more complete picture of the cellular heterogeneity. This leap in technology development makes it possible to determine which cell types and states are contributing to disease progression and therapeutic responses.
One current objective is to unravel the composition of infiltrating myeloid cells in head and neck cancers, the area of immune oncology, in order to identify novel prognostic and immunotherapeutic targets. We further develop cellular 3D cellular assays that can be employed for functional studies.
We are also involved in the IMI project ImSAVAR (Immune safety avatar: nonclinical mimicking of the immune system effects of immunomodulatory therapies), which aims to develop innovative model systems that can be used to assess efficacy and safety of immunomodulatory therapies in the early drug development stages, and to identify biomarkers for diagnosis and prediction of immune-mediated safety issues.
Another focus area is the role of DCs in the sensitization process, and we investigate the mechanisms of DC activation caused by chemical challenge. We are currently interested in the effect of complex mixtures in our developed assays, identification of adverse pathways involved in sensitization and correlation of specific pathway usage to potency predictions. Commonly used technologies include multicolour flow cytometry, single-cell sorting, immune cell profiling using transcriptomics and proteomics, 2D and 3D cell cultures, and biostatistical approaches for multivariate analysis.
Our main research activities include: