Immune system modulation
Cancer progression occurs through suppression and evasion of anti-tumour immune responses. On the other hand, transplantation rejection is the result of immune response towards the transplanted organ. Efficacy of cell therapy is limited by the unpredictable performance of transferred immune cells as they can change from an immune-tolerant state to an immune-active one. Under the aegis of the MODICELL (Targeted modulation of immune-system responses in cell therapies) project, scientists set out to find ways to reliably enhance immune response or immune tolerance on demand. During the first two years of the project, scientists established strategies to develop potent dendritic cells for tumour vaccination as well as induce immune tolerance in vitro. A fully automated RNA sequencing analysis pipeline is now readily available that can be used by other projects. Project partners also restructured their Reactive Animation models to enable visualisation with simulation, and developed a user interface to input different scenarios and cells. Experiments are ongoing and researchers are collecting high-throughput data for bioinformatics analysis. Already, they have identified experimental conditions and combinatorial tolerising approaches that produce a robust regulatory phenotype. They have also gained deeper insight into the role of hypoxia in immune regulation. Next-generation sequencing of the T cell receptor (TCR) in 12 glioblastoma patients showed differences in TCR patterns. These differences were linked to higher survival and response to cancer immune therapy (CIT). This is a key finding as TCR sequencing could prove to be the means for generating effective anti-tumour immune responses with dendritic cell CIT. MODICELL will continue efforts to elucidate differences in dendritic and T cell regulation during normal and cancerous conditions to optimise tumour vaccination. Through the creation of a MySQL database, they intend to generate models to study the effect of CIT in vaccinated patients. Successful project outcomes could improve cancer and transplant patient outcomes through the development of effective cell-based therapies. The knowledge engendered could also help resolve other immune-mediated disorders.
Keywords
Immune system, cancer, transplantation, tumour, RNA sequencing, T cell
