Their groundbreaking work on peripheral tolerance opened new paths for treating cancer, autoimmune diseases, and improving transplant success.
The 2025 Nobel Prize in Medicine has been awarded to Americans Mary E. Brunkow, Fred Ramsdell, and Japanese scientist Shimon Sakaguchi for their groundbreaking research on how the body regulates the immune system.
The Nobel Committee announced that the trio was recognized for their “discoveries on peripheral immune tolerance.”
Marie Wahren-Herlenius, professor at the Karolinska Institute, explained that their findings deepened our understanding of “how we control our immune system to fight microbes without triggering autoimmune diseases.”
Their discoveries established the foundation of a new field of study —peripheral tolerance— which has led to major medical advances in the treatment of cancer and autoimmune diseases.
It also offers new hope for more successful organ transplants and reduced rejection risks. Several therapies inspired by their work are currently in clinical trials.
In 1995, Shimon Sakaguchi identified a new class of T cells, a breakthrough that transformed immunology. At that time, most scientists believed immune tolerance depended solely on the elimination of harmful cells in the thymus —a process called central tolerance.
Sakaguchi revealed that an additional mechanism, peripheral tolerance, plays a vital role in preventing autoimmune reactions and maintaining immune balance.
Meanwhile, Mary E. Brunkow and Fred Ramsdell made a key discovery in 2001 that illuminated the genetic basis of certain autoimmune diseases. They found that a specific strain of mice prone to such conditions carried a mutation in a gene they named Foxp3.
The scientists also demonstrated that mutations in the human equivalent of this gene cause a severe autoimmune disorder known as IPEX syndrome.
Their collective work revealed the mechanisms that allow the immune system to tolerate the body’s own tissues while defending against pathogens.
The Nobel Committee emphasized that Brunkow, Ramsdell, and Sakaguchi’s research has transformed modern medicine, paving the way for more effective therapies in cancer treatment, autoimmune diseases, and organ transplantation.
Each laureate will receive a diploma, a gold medal, and a cash award of $1.2 million.
