Core Viewpoint - The article discusses the groundbreaking discoveries by Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi, who were awarded the 2025 Nobel Prize in Physiology or Medicine for their work on regulatory T cells (Treg cells) and their role in peripheral immune tolerance, significantly enhancing the understanding of immune regulation and its implications for autoimmune diseases and cancer [3][11][19]. Group 1: Key Discoveries - The researchers identified and defined CD4+ CD25+ FOXP3+ regulatory T cells (Treg cells) and their critical role in controlling self-reactive responses, leading to the establishment of a new field of study in immune tolerance [3][11][19]. - Shimon Sakaguchi made the first key discovery in 1995, demonstrating that immune tolerance is more complex than previously thought, revealing a previously unknown T cell type that protects against autoimmune diseases [11][14]. - In 2001, Brunkow and Ramsdell discovered a gene mutation in specific mouse strains that made them prone to autoimmune diseases, naming the gene Foxp3, which is also linked to a severe autoimmune disease in humans known as IPEX syndrome [14][18]. Group 2: Implications and Future Directions - The findings of these researchers have opened new avenues in the treatment of cancer and autoimmune diseases, with potential to improve organ transplant success rates, as therapies based on their discoveries are currently in clinical trials [19][20]. - There are over 200 clinical trials involving Treg cells aimed at treating common diseases such as asthma, inflammatory bowel disease, and skin-related conditions, or improving organ transplant outcomes [23]. - The achievements of Brunkow, Ramsdell, and Sakaguchi highlight the importance of scientific perseverance and the integration of clinical observations with basic research, paving the way for enhanced understanding and therapeutic applications of Treg cells [24].