They understood how the immune system is kept in check: The 2025 Nobel prize in physiology or medicine
- This year’s Nobel prize in physiology or medicine was awarded to researchers who discovered regulatory T cells (Tregs), whose role is to suppress the excessive immune response.
- Their discovery paves the way for innovative therapies, including antibody-drug conjugates that modulate the activity of immune system to fight cancer.
This year’s Nobel prize in physiology or medicine goes to Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi for their seminal discoveries concerning peripheral immune tolerance.
Their groundbreaking work has defined the critical role of CD4+CD25+FOXP3+ regulatory T cells (Tregs) in suppressing aberrant immune responses, thereby preventing autoimmunity while enabling effective pathogen clearance. The discoveries stemmed from meticulous experiments challenging the dominance of central tolerance. Sakaguchi’s work in Japan revived the suppressor T cell concept through neonatal thymectomy studies in mice, revealing CD4+CD25+ T cells as immune regulators that prevent autoimmunity when transferred. Meanwhile, Brunkow and Ramsdell’s positional cloning of the scurfy mutation identified Foxp3 as the master regulator, linking it to human IPEX, a rare genetic autoimmune disorder, and proving its essential role in Tregs development and function.
This research has profound implications for immunology, elucidating how Tregs maintain homeostasis by modulating effector T cell activity and cytokine production. It also spurred the development of novel biologics modulating the activity of Tregs, which could be used to suppress autoimmunity in diseases such as rheumatoid arthritis, inflammatory bowel disease, and type 1 diabetes. Conversely, strategies to deplete Treg cells or reduce their activity could prove useful in oncology to enhance anti-tumor immunity, in a similar manner to the widely employed immune checkpoint inhibitors. Antibody-drug conjugates (ADCs) and immunotoxins, typically engineered to directly kill cancer cells, are top candidates here. Several ADCs that target tumour-inflitrating regulatory T cells instead of cancer cells have been developed and are currently being evaluated in clinical trials. In total, more than 200 trials involving Tregs are underway and the scientific community eagerly awaits their results.
Read more about the scientific work of the Nobel prize laureates in the press release.
For those interested in learning more about drug conjugates targeting regulatory T cells, we recommend the Nature article.
Prepared by:
Adam Tuszyner
Regulatory Compliance Specialist