Återställande av antitumörimmunitet genom direkta omprogrammeringsstrategier för dendritiska celler

More than 1.5 million people die of cancer every year just in Europe. Therefore, it is imperative to develop new anti-cancer treatments. In the past years, researchers have investigated cancer immunotherapies – treatment strategies that engage patient’s own immune system to fight cancer. The immune system plays a complex role in development and progression of cancer. In the beginning of cancerous growth, the immune system can recognize tumour cells as foreign due to molecular signs that indicate that the cells are not normal and do not belong to ourselves. These molecular signs are designated by tumour antigens. During disease progression, cancer cells adopt new strategies that allow them to hide and effectively escaping the immune system’s radar by, for example, masking these tumour antigens.
Dendritic cells are important players of the immune system. They act as a patrolling soldier in our body, whose work is to scan foreign antigens, such as those coming from cancer, bacteria or virus, and eat them. After eating these antigens, they reduce them to smaller portions and present them at their surface to other soldiers, the effector immune cells such as T and B cells. Effector immune cells can travel much faster throughout the blood system and reach the places where these antigens can be found to hunt and destroy every cell that contains them. In the end, the role of dendritic cells in cancer is to present tumour antigens and help T-cells to reach the cancer environment so that the latter can kill tumour cells. However, as mentioned before, cancer cells are clever and avoid being detected first by dendritic cells and hide from them.
Our group identified 3 specific proteins which bind DNA – transcription factors – that can change the fate of one cell, e.g. skin cell, towards a dendritic cell. This process is called cellular reprogramming in which an adult cell converts into another. In our specific case, skin cells can reprogram into dendritic cells and function as one too. They have the capacity to eat antigens and present them and activate the effector immune cells to elicit an immune response. This important feat has led to the hypothesis: can we reprogram cancer cells to act as dendritic cells and show their own antigens? The answer is yes!
In this project, we are changing the fate of tumour cells and convert them into dendritic-like tumour antigen presenting cells. This strategy allows us to force cancer cells to reveal their antigens at the cell surface and make them once again visible to the effector immune cells. Moreover, they not only show their own antigens but also snack on other cancer cells antigens and present them too. We hope that with this novel immunotherapy, dendritic-like tumour cells will work as secret agents inside the tumour – forcing them out of their hiding place to seek the immune system.