Core Insights - The 2025 Nobel Prize in Physiology or Medicine was awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their groundbreaking discoveries in peripheral immune tolerance, which have opened new research avenues and advanced therapies for cancer and autoimmune diseases [1][6]. Group 1: Immune System Functionality - The immune system protects humans from thousands of viruses and bacteria daily, and its ability to distinguish between pathogens and self-cells is crucial for survival [1]. - T cells possess a unique protein called T cell receptors that act as sensors to identify whether the body is under attack, with the potential to create over 10^15 different T cell receptors [1][2]. Group 2: Research Breakthroughs - In the 1980s, researchers identified a selection process called "central tolerance" that eliminates T cells that mistakenly attack the body's own tissues during their maturation in the thymus [2]. - Shimon Sakaguchi proposed the existence of "regulatory T cells" as a mechanism to calm other T cells, leading to the discovery of this new T cell type after over a decade of research [2][5]. Group 3: Genetic Discoveries - In the 1940s, researchers discovered "scurfy" mice that suffered from severe immune system issues due to T cell attacks on their organs, leading to the investigation of the underlying genetic causes [3][4]. - Mary E. Brunkow and Fred Ramsdell identified the Foxp3 gene, which is linked to the IPEX autoimmune disease and is crucial for the development of regulatory T cells [4][5]. Group 4: Therapeutic Implications - The findings regarding regulatory T cells have spurred the development of potential new therapies, including the isolation and amplification of these cells from patients to enhance their immune response [6]. - Researchers are exploring methods to modify regulatory T cells to target specific organs, thereby protecting them from immune system attacks [6].