Tolerant ratios: the Nobel Prize in medicine was awarded for research on immunity

The research of scientists who received the Nobel Prize in Physiology or Medicine in 2025 laid the foundations for a deep understanding of the mechanisms of development of autoimmune diseases, and also made it possible to introduce new cancer treatments. The discoveries made by American researchers Mary E. Brankow, Fred Ramsdell and Japanese scientist Shimon Sakaguchi will help improve the efficiency of organ transplantation. What the Nobel Committee awarded the award for and how doctors around the world use these achievements in practice — in the Izvestia article.

Who won the Nobel Prize in Physiology or Medicine?

This year's Nobel Prize winners in Physiology or Medicine are scientists Mary E. Brankow (Seattle, USA), Fred Ramsdell (San Francisco, USA) and Shimon Sakaguchi (Osaka, Japan). This was announced by the Nobel Committee on October 6. The award was given "for discoveries concerning peripheral immune tolerance," which prevents the body from harming the immune system.

The laureates have identified the defenders of the immune system — regulatory T-cells that prevent immune cells from attacking their own body, according to an official press release from the Karolinska Institute.

"Their discoveries have played a crucial role in our understanding of how the immune system functions and why not all of us develop serious autoimmune diseases," said Olle Kempe, chairman of the Nobel Committee.

— This team is engaged in extremely important fundamental research on the mechanisms of resistance and regulation of the peripheral immune system. The significance of their discoveries, especially in the context of oncological, autoimmune diseases and the process of tumor formation (tumorogenesis), has been rightly recognized by the scientific community," Philip Maksimov, senior researcher and head of the Laboratory of Structural and Functional Research of innovative antitumor Drugs at MIPT, explained to Izvestia.

This topic is of great importance, since it is known that the weakening of peripheral immunity can lead to malignancy of abnormal cells and the development of tumors. The role of the immune system in the pathogenesis of autoimmune diseases is equally important, when it begins to attack the body's own tissues and cells, the scientist said.

In 1995, Shimon Sakaguchi made the first key discovery. At that time, many researchers were convinced that immune tolerance developed only by destroying potentially dangerous cells of the body's defense system in the thymus through a process called central tolerance. Sakaguchi showed that the immune system is more complex and discovered a previously unknown class of immune cells that protect the body from autoimmune diseases.

Mary E. Brankow and Fred Ramsdell made another key discovery in 2001, providing an explanation for why a particular line of mice is particularly vulnerable to autoimmune diseases. They found a mutation in a gene in the animals, which they named Foxp3. They also showed that mutations in the human equivalent of this gene cause a serious autoimmune disease called IPEX syndrome.

This is a rare, severe hereditary disease that manifests itself in early childhood, said Arseniy Yuzhalin, head of the scientific group of the III category of the Scientific Center for Translational Medicine at Sirius University of Science and Technology. Its essence is that the human immune system attacks its own organs and body tissues. The skin, intestines, and endocrine system are primarily affected, leading to rashes, diarrhea, and diabetes. The treatment of such patients is quite complicated.

—And the research obtained by the current Nobel laureates has allowed us to correctly identify the nature of this disease and develop appropriate treatment methods," the researcher emphasized.

Two years later, Shimon Sakaguchi linked these discoveries together. He proved that the Foxp3 gene controls the development of cells, which were identified in 1995. These cells, now known as regulatory T cells, control other immune cells and ensure our immune system's tolerance to its own tissues.

— They all worked on the study of transphyric tolerance. Shimon Sakaguchi has discovered a previously unknown class of immune cells that protect the body from autoimmune diseases. These were the elusive T-suppressors. And in 2001, Mary Brankow and Fred Ramsdell provided an explanation of how these cells work," Mikhail Bolkov, a researcher at the Institute for the Study of Aging at the Russian State Scientific and Clinical Center of the Pirogov Russian National Research Medical University, told Izvestia.

According to the expert, since then the cells have been called T-regs (Treg), or T-regulatory lymphocytes. It is now also known about B-regulatory lymphocytes, and many different subtle points about how tolerance to one's own microbiota is fostered, as well as how it is disrupted by autoimmune diseases.

Immune tolerance studies

Peripheral immune tolerance exists in the human body to maintain an immune balance between pro- and anti-inflammatory immune responses. Its violation leads to autoimmune and oncological diseases, said Ekaterina Astakhova, a researcher at the Center for Living Systems at MIPT.

— The discovery laid the foundation for new treatments for autoimmune diseases.For example, personalized cell therapies based on T-regulatory cells are being actively developed for the treatment of autoimmune diseases, such as type 1 diabetes," the specialist said.

Scientists have shown that the immune system has its own "brakes" that prevent the immune system from attacking its own body, as occurs in autoimmune diseases, Albert Rizvanov, head of the Personalized Medicine Center of Excellence at Kazan (Volga Region) Federal University, explained to Izvestia.

— Regulatory T cells were discovered by Shimon Sakaguchi, and the "main switch" of their program, the FOXP3 gene, was discovered by Mary E. Brankow and Fred Ramsdell. If it breaks down, severe autoaggression (IPEX) develops. This knowledge is already being introduced into medicine. By strengthening Treg, doctors seek to extinguish autoimmune attacks and increase the success of transplantation. In oncology, on the contrary, it is necessary to remove excessive inhibition in order to enhance the antitumor response. A number of approaches are already in clinical trials," the scientist noted.

The award-winning research has already yielded practical results. For example, they underlie cancer therapy with checkpoint inhibitors. This method is used to treat melanoma, tumors of the kidneys, lungs and other organs. It helps to neutralize the ability of malignant tumors to block the immune response. Thanks to this, the body's defense system "sees" the tumor and begins to fight it, Alexey Grachev, a professor at Skoltech, head of the Laboratory of Tumor stromal cell Biology at the Blokhin Research Institute of Carcinogenesis at the Russian Ministry of Health and a member of the Russian National Science Foundation's Expert council, told Izvestia.

— Our understanding of how a tumor escapes from immune surveillance is based, among other things, on these studies. They were completed quite a long time ago, but they came into widespread practice about five years ago. This is why the Nobel Prize was awarded," the expert said.

According to him, this scientific field has not yet been exhausted. Immune tolerance is based not only on the T cells described by the laureates, but also on monocytes, macrophages, B cells, and others. If we can cover the entire spectrum and evaluate the contribution of each type of immune system cell to the mechanism of tolerance, this will open up many related areas for further development and the creation of new types of therapies.