An international research team, led by the University of Coimbra (UC) and Lund University (Sweden), has identified new “recipes” for reprogramming cell models and converting them into different subtypes of dendritic cells - immune system cells which, by identifying and capturing threats, play a decisive role in responding to diseases. Scientists believe that this discovery could pave the way for more effective immunotherapy treatments, adapted to each patient and type of cancer, and even create strategies to combat other diseases, such as diabetes and rheumatoid arthritis.

It was in search of new information to reprogram skin cells and cancer cells into subtypes of dendritic cells that the team of scientists managed to identify two new combinations of three factors, which make it possible to regulate the identity of the cells. “These combinations work as ‘recipes’ to convert a cell into another cell type; and, specifically, from the new data for cell reprogramming that we have revealed in this study, it is possible to more effectively generate two subtypes of dendritic cells that have not yet been explored in immunotherapy: type 2 and plasmacytoid,” reveals Carlos-Filipe Pereira, a researcher at the University of Coimbra Center for Neuroscience and Cell Biology (CNC-UC) and the Centre for Innovative Biomedicine and Biotechnology (CiBB).

The leader of this research explains that “as different tumors respond differently to treatments, identifying the ‘recipes’ that give rise to each subtype of dendritic cells opens the way to personalized immunotherapy treatments, adapted to each patient and the type of cancer they face.” “This knowledge can bring us closer to more effective immunotherapies, helping to reduce the likelihood of therapeutic failure and speed up the development of new strategies against cancer,” says Carlos-Filipe Pereira.

In immunotherapy, the immune system of the person who is ill is used to fight cancer. In this type of treatment, the immune system is taught to recognize and attack cancer cells to destroy the tumour. In this process, dendritic cells “are the ‘teachers’ and they are essential for guiding and triggering effective responses, although the use of their different subtypes in immunotherapy is still limited,” explains the professor at Lund University. Although immunotherapy is seen as one of the most promising areas of medicine, in the case of oncology “a significant proportion of cancer types and patients do not respond to this treatment,” he adds.

Alongside the discovery of this new information - published in a scientific article in the journal Immunity - the researchers were also able to demonstrate that “different subtypes of dendritic cells exert different beneficial effects in animal models of melanoma and breast cancer,” says Carlos-Filipe Pereira. “Thus, this study does not provide a single solution but opens up the possibility of adapting the therapeutic strategy to the tumour subtype, bringing us closer to more personalized and effective immunotherapies,” he adds.

In addition to treating cancer, this study could also contribute to cellular reprogramming aimed at other diseases, as the research leader reveals: “this work not only deepens our understanding of the role of dendritic cells in cancer, establishing new paths for immuno-oncology, but also opens doors to the development of personalized therapies in various diseases - such as diabetes or rheumatoid arthritis.”

Previously, the research team of Carlos-Filipe Pereira (who leads CNC-UC's research group in Immune Cell Reprogramming) had already identified factors capable of converting skin cells into subtype 1 dendritic cells. With the data from this new study, the researchers have taken another step towards assessing an approach that “allows specific subtypes of dendritic cells to be generated in the laboratory, which can increase the effectiveness of immunotherapy,” the scientist stresses.

The first author of the study Anchored screening identifies transcription factor blueprints underlying dendritic cell diversity and subset-specific anti-tumor immunity is Luís Henriques-Oliveira, a student on the UC PhD Programme in Experimental Biology and Biomedicine and a researcher at CNC-UC and CiBB.

Researchers from the University of Calgary (Canada), the Technical University of Denmark, Asgard Therapeutics (Sweden), and the Memorial Sloan Kettering Cancer Center (United States) also took part in the study.

The scientific article is available here.

Catarina Ribeiro with CNC-UC