In order to reprogram readily available cells into specific immune cells that fight various diseases, one must know the “recipe” for the transformation. Researchers at Lund University have now created a library of the 400 factors needed for reprogramming and have begun the work of finding the right combination – the recipe – for each type of immune cell.
Our immune system consists of different types of cells that specialise in different functions to protect us from disease. Normally, the immune system is very good at finding and destroying viruses, bacteria and cancer cells. But at the same time, these intruders can also develop strategies to evade the immune system’s attacks.
– Immunotherapy is a group of treatments that help the body defend itself by strengthening or controlling the immune system. In cancer, current approaches include, for example, CAR-T cell therapy, where a patient’s own T cells are genetically modified to better find and kill cancer cells. It is one of the most promising methods in modern medicine, says Ilia Kurochkin, postdoc at Lund University and first author of the study.
Despite advances, not all patients respond to current treatments. In addition, despite their importance for immunotherapy, many of our immune cells are rare and difficult to extract from the patient’s blood. Being able to reprogram easily accessible cells into rare immune cells is therefore promising for future immunotherapies, giving hope for the unresponsive patients of the current forms of immunotherapy.
– However, progress has been limited because we still do not fully understand the factors that control the identity and function of cells. To convert a more accessible cell – for example, a skin cell – into a specific immune cell, we first need to know which factors are needed for reprogramming and generate that particular identity, says Ilia Kurochkin.
The researchers therefore wanted to develop a technique to identify the factors needed to reprogram rare immune cell populations. They created a library of over 400 immune-related factors, each labelled with a unique DNA barcode. Using this system, they were then able to test thousands of combinations simultaneously and track which ones triggered the conversion to specific immune cells.
– It took us four years to develop the screening technique and complete the library. This is the foundation for subsequently creating “recipes” for reprogramming immune cells. Depending on the type of cell you want to reprogram that can be harnessed to treat multiple diseases, you go to the “recipe book” to see the instructions for reprogramming,” says Filipe Pereira, Professor of Molecular Medicine at Lund University, who led the study.
The researchers have developed a platform to systematically discover such “recipes” and have already identified recipes for six different types of immune cells. The goal is to continue finding recipes for reprogramming more types of immune cells and their functional states. The method also made it possible for the first time to produce immune cells that were previously not accessible through reprogramming, such as natural killer cells (NK cells), which are crucial for fighting cancer cells. In the future, the team aims to extend this technology beyond cancer to other diseases involving the immune system.
The goal is to create “recipes” for reprogramming all our immune cells, which can accelerate the development of new therapeutic strategies against cancer, autoimmune diseases and tissue repair that are tailored to each individual’s immune system. The next step is to prove the principle of harnessing the immune cell reprogramming beyond cancer and test new combinations in autoimmune disease models.”
Filipe Pereira, Professor of Molecular Medicine, Lund University
Immune cellular reprogramming
Immune cellular reprogramming is a process that can convert readily available cells into specific immune cells that fight various diseases. The key factors for this reprogramming have so far only been mapped for four of the body’s more than 70 types of immune cells. Researchers at Lund University have now created a library of more than 400 immune factors and developed a technique for finding the right combinations – the ‘recipes’ – for generating different immune cells on a large scale.
Source:
Journal reference:
Kurochkin, I., et al. (2026). A combinatorial transcription factor screening platform for immune cell reprogramming. Cell Systems. doi: 10.1016/j.cels.2025.101457. https://www.cell.com/cell-systems/fulltext/S2405-4712(25)00290-X
