Researchers identify genetic toolkit to reprogram cells into immune sentinels

An international team led by researchers at Lund University in Sweden has identified the molecular tools needed to reprogram ordinary cells into specialized immune cells. The discovery, published in Immunity, could pave the way for more precise and personalized cancer immunotherapies.

The team has taken an important step toward harnessing the immune system to fight cancer. Their work describes how they identified a genetic toolkit that programs two powerful subtypes of dendritic cells – key sentinels of the immune system. Dendritic cells are a diverse group of immune cells that act as the body’s “teachers”, guiding the immune system to recognise and attack threats such as viruses, bacteria or tumours. Each subtype triggers different immune responses, adapting to the nature of the threat. Supplying patients with dendritic cells designed to target their cancer could make treatments more precise and powerful.

Understanding how this cellular diversity is generated during the process of development has long been a mystery. Scientists have known some of the so-called transcription factors – proteins that switch genes on and off – that control these cells’ development, but how these factors work together to create different dendritic cell types has been unclear.

Now, the team of researchers behind this publication has carried out a systematic mapping of the routes to dendritic cell identity. By testing 70 different transcription factors and seeing how they could reprogram ordinary cells into dendritic cells, they identified two distinct toolkits that reprogrammed skin or cancer cells into powerful dendritic cell subtypes. Advanced gene analysis revealed that these factors, early in the process, open different parts of the genome and thereby determine the different cells’ fate.

“Through cellular reprogramming, one cell type can be converted into another. We identified two specific combinations of three factors that act as tools to build two dendritic cell types: conventional type 2 dendritic cells and plasmacytoid dendritic cells,” says Filipe Pereira, professor of molecular medicine at Lund University, who has led the research.

When tested in mouse cancer models, one engineered dendritic cell subtype triggered strong immune responses against melanoma, while others acted against breast cancer, in ways similar to their natural counterparts. While still in the early stages, the findings suggest that supplying patients with dendritic cells tailored to their cancer could, in the future, make immunotherapy more powerful and more personal.

Immunotherapy is one of the most promising areas in medicine, but many patients still do not respond. Our work shows that by generating specific dendritic cell types, we can better match the immune response to a specific cancer. This is an early step, but it points to the potential for truly personalised immunotherapy.”

Filipe Pereira, professor of molecular medicine at Lund University

Beyond cancer, the discovery that dendritic cell diversity can be programmed may have applications in autoimmune diseases. Some dendritic cells naturally “calm” the immune system, and reprogramming toward these anti-inflammatory subtypes could one day help treat conditions where the immune system attacks the body.

The study provides the first systematic blueprint of the immune system’s toolkit for dendritic cell reprogramming, a resource that may help researchers design better treatments for cancer and immune disorders.