2025 Nobel Prize in Medicine to Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi for identifying the "security guards of the immune system."

The Karolinska Institute in Stockholm recognizes laureates for discovering regulatory T cells, which prevent immune cells from attacking our own bodies.

The Karolinska Institute in Stockholm (Sweden) awarded this Monday the Nobel Prize in Physiology or Medicine to American scientists Mary Brunkow and Fred Ramsdell, and to Japanese scientist Shimon Sakaguchi “for their discoveries concerning peripheral immune tolerance.” The laureates identified the “security guards of the immune system,” regulatory T cells, which prevent the immune system from attacking our own bodies, the committee explained.

"Their findings have been fundamental to our understanding of how the immune system works and why not all humans develop autoimmune diseases," he specified. Olle Kampe, president of the jury.

The key discovery in this field was made by the Japanese immunologist Shimon Sakaguchi In 1995, after years of research without recognition in his field, the researcher managed to isolate for the first time the regulatory T cells, a type of essential lymphocyte that modulates the activity of the rest of the immune system, and protects the body from autoimmune diseases.

Until then, most researchers were convinced that immune tolerance only developed because potentially harmful immune cells were eliminated in the thymus, through a process called central tolerance. This gland, located in the chest, below the sternum, is where the different types of T lymphocytes are generated and matured. These are a class of white blood cells that are part of the adaptive immune system that protects us from infections, pathogens, and other external aggressions. Sakaguchi, 74, a researcher at Osaka University, was the first to demonstrate that, in addition to the already known types of lymphocytes (killer, helper, antibody-producing, etc.), there is this new type of modulating cells that are essential for the proper functioning of the whole system.

Americans Mary Brunkow, of 61 years, and Fred Ramsdell, aged 60, have been awarded for their research on autoimmune diseases, specifically on the gene Foxp3. The scientists were focused on studying dandruffed mice that suffered from a hereditary autoimmune disease that caused their skin to flake. They identified the mutation in this gene that was responsible for this disease. Brunkow, a molecular biologist, and Ramsdell, an immunologist, also showed that other mutations in foxp3 They cause serious autoimmune diseases in humans. Among them is IPEX syndrome, linked to the X chromosome and suffered only by children, causing death in their first years of life.

Two years after these discoveries, Sakaguchi demonstrated that this gene governs the production of regulatory T cells, which he named after them. These cells are essential for the rest of the immune system to tolerate the body's own tissues and not attack them. "I believe this will encourage immunologists and physicians to use regulatory T cells to treat various immunological diseases," Sakaguchi said in a statement reported by the prize organizers.

The jury emphasized that the work of these three scientists has opened a new field and advances future treatments for cancer and autoimmune diseases. Currently, these regulatory cells extracted from the thymus have been essential in preventing transplant rejection, and clinical trials are already underway to demonstrate their effectiveness as a generalized treatment.

Ramsdell is a scientific advisor to Sonoma Biotherapeutics, the company he co-founded in 2019 in the United States to develop treatments for rheumatoid arthritis and other autoimmune diseases based on regulatory T cells. Brunkow works at the Institute for Systems Biology in the United States.

Irene's Heart

Living proof of the medical importance of this discovery is Irene, a five-year-old Spanish girl who was the first in the world to receive treatment with regulatory T cells to make the heart transplant she needed possible. The key to success was not discarding her thymus after surgery, as was commonly done, but using it as a source of cells that were later used for treatment.

The same procedure has already been used in nine transplanted babies, explains Dr. Rafael Correa, director of the Immunoregulation Laboratory at the Gregorio Marañón Hospital in Madrid and leader of this pioneering line of research. "We have demonstrated that it is a safe, effective therapy capable of preventing acute rejection after a transplant, as it restores the capacity for immunological tolerance," he emphasizes. These cells "have immense potential" as a treatment, Correa emphasizes, for many immune-mediated diseases such as diabetes, allergies, as well as neurodegenerative and autoimmune diseases.

This year's Nobel Prize in Medicine has another strong connection to Spain. Giovanna Roncador, a scientist at the Spanish National Cancer Research Centre (CNIO), developed the antibodies needed to detect the gene in 2005. foxp3. Their sale to immunology laboratories around the world is one of the main sources of royalty income for the CNIO. “This development marked a turning point in the study of regulatory T cells,” explains Giovanna Roncador. “For the first time, we were able to clearly distinguish these cells in both tissues and cells, which furthered our understanding of their role in immunology and in pathologies such as cancer and autoimmune diseases.”

Thanks to this and other similar breakthroughs, Roncador is one of the highest-earning scientists in Spain. But paradoxically, she doesn't receive a single euro for her discoveries due to complex bureaucratic hurdles. The scientist explains that she has received a commitment from the Ministry of Science, Innovation, and Universities that the problem will be resolved "before the end of the year," putting an end to a conflict that has existed since 2020, she explains.

Unlike other lymphocyte therapies, such as CAR-T cells, in this case the cells extracted from the patient are not modified, as they fully retain their ability to modulate the immune system and prevent negative reactions. This makes it possible to use thymus tissue extracted from infants as a source of cells not only for the infants themselves, but potentially also for other adult patients, a therapy that Correa's team is already testing in a pioneering clinical trial.

“It's increasingly clear that immunology is related to almost every disease we can think of, and this Nobel Prize is proof of that,” emphasizes Marcos López-Hoyos, former president of the Spanish Society of Immunology. “Our immune response is like a juggler, as it must activate and respond to any external aggression, but also shut down to maintain balance. In this, peripheral immunity generated by regulatory T cells is essential,” explains the immunologist.

The physician and researcher emphasizes that until 1995, "no one" supported the Japanese scientist Sakaguchi's thesis. After his seminal discoveries, the existence of these regulatory cells became widely accepted, and today, "all immunologists study their genetic characteristics due to their important role in regulating" the immune system, he adds.

The discovery awarded this Monday is also being analyzed for future approaches to cancer treatment. "We are exploring new treatments that suppress the activity of these regulatory T lymphocytes in the context of cancer immunotherapy," explains Ignacio Melero, an immunologist at the University of Navarra Clinic. "At the moment, we see antitumor activity, although there are safety concerns due to the triggering of autoimmune phenomena," he explains. In this sense, Melero believes this Nobel Prize is "surprising," given that for now it has no clear and approved "medical application," but is more of an award for a basic discovery of the immune system.

Since 1901, the Nobel Prize in Physiology or Medicine has recognized 229 researchers, 14 of whom have been women.

Last year, American researchers Victor Ambros and Gary Ruvkun received the prize for discovering microRNAs and describing their role in "post-transcriptional gene regulation." The discovery by Ambros, a researcher at the University of Massachusetts (United States), and Ruvkun, affiliated with Massachusetts General Hospital, reveals a completely new principle of genetic regulation essential for the development and functioning of multicellular organisms, including humans. In 2023, it was awarded to Katalin Karikó and Drew Weissman for the COVID vaccine, and in 2022 to Svante Pääbo for unraveling the genetics of extinct humans.

This is the first Nobel Prize awarded this week, followed by the Physics Prize on Tuesday and the Chemistry Prize on Wednesday. Each prize is worth 11 million Swedish kronor, approximately one million euros.

Source: EL PAÍS