“These discoveries have opened up a new research field and allowed for a better understanding of autoimmune diseases and cancer, and have already inspired treatments currently in clinical trials”. Tiago Fernandes, a professor at Técnico and researcher at the Institute for Bioengineering and Biosciences (iBB), comments on the implications of the work carried out by Mary Brunkow, Fred Ramsdell and Shimon Sakaguchi, who were awarded the Nobel Prize in Physiology or Medicine 2025. “The Nobel Prize is fully justified. Before this research, it was not understood why some individuals developed serious autoimmune diseases”, he adds.

Tiago Fernandes answers some questions about the work awarded this year by the Karolinska Institute.

How would you explain the importance of the award-winning work? How does it justify the Nobel Prize?

Tiago Fernandes (TF) – Every year, I follow the announcements of the Nobel Prize Committee with great interest. This year, the committee decided to award the Nobel Prize in Physiology or Medicine to three researchers – Mary Brunkow, Fred Ramsdell and Shimon Sakaguchi – for their discoveries on how the immune system distinguishes between the ‘enemies’ it must attack (pathogens) and the ‘friends’ it must protect (the body’s own cells). In particular, they discovered a specific type of cell called regulatory T cells (or Tregs).

Tregs function like referees in a football match: while the other cells of the immune system are focused on attacking and defending against diseases and invaders, Tregs are responsible for ensuring that the rules are followed, preventing the immune system from committing fouls, such as attacking the body’s own cells by mistake. In this way, Tregs suppress unnecessary or dangerous responses, preventing collateral damage.

Before these discoveries, it was thought that T cell control of the immune system happened primarily in the thymus during maturation. These researchers showed that there is an additional layer of control beyond the thymus, known as peripheral immune tolerance, provided by Tregs.
In my opinion, this fully justifies the Nobel Prize. Before this work, it was not understood why some people developed severe autoimmune diseases. These discoveries have opened up a new research field and led to a better understanding of autoimmune diseases and cancer, and have already inspired treatments currently in clinical trials.
The recognition of this work with the Nobel Prize is also a tribute to decades of basic research on a topic that seemed “simple” but has proved to be fundamental to precision medicine, cell therapies, cancer immunotherapy and the management of autoimmune diseases.

What scientific advances have resulted from the work of these researchers? What benefits could they bring in the future?

TF – There are already clinical trials exploring Treg cell-based therapies to treat autoimmune diseases, transplant patients (to prevent rejection) and some types of cancer.

This work has opened the door to understanding autoimmune diseases such as type 1 diabetes and lupus. We also find potential applications in the context of cancer. For example, it may be possible to learn how to “switch off” Tregs so that we can better selectively attack tumour cells.
Finally, in the context of organ and cell transplantation, it may be possible to act on or manipulate Tregs to reduce the rejection of cell or organ grafts, minimising the side effects of transplantation.

What other advances in medicine would you like to have seen recognised with this year’s Nobel Prize?

TF – That’s an open and very personal question. I believe that, historically, the Nobel Prize has always been limited in scope. Many worthy advances are overlooked every year.
Personally, in the near future, I would like to see recognition of the progress made in the field of neurodevelopmental disorders and advances in understanding the neurobiology of autism spectrum disorders.
That said, I would like to emphasise that this year’s prize highlights a highly crosscutting and impactful scientific field with the potential to benefit numerous areas.

How does your work relate to that of the award winners?

TF – Considering the work I do, together with other colleagues from Técnico and the Department of Bioengineering, I see a direct relationship between these developments and our research: understanding the control of the immune response is fundamental to the success of transplantation and the clinical use of cells generated in vitro, both to avoid rejection and to prevent autoimmune complications.
The discovery of regulatory T cells (Tregs) opens up the possibility of promoting immune tolerance in stem cell-derived tissue transplants, enhancing safety and therapeutic efficacy in these cases.
It is expected that techniques capable of stimulating or modulating these cells will be integrated into clinical protocols to minimise adverse post-graft effects in both paediatric and adult patients, addressing important challenges in regenerative and personalised biomedicine.