New Study Identifies Molecule That Promotes Thymus Regeneration

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Bottom line: A new study from Memorial Sloan Kettering’s (MSK) Marcel van den Brink— in collaboration with Jarrod Dudakov, PhD, at the Fred Hutchinson Cancer Center — has identified a molecule that promotes thymus regeneration. The results could pave the way toward treatments that could one day help rejuvenate an aging or damaged thymus.

Journal: “Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration” appears in the January 12, 2018 issue of Science Immunology.

Authors: MSK’s Marcel van den Brink, MD, PhD, was the senior corresponding author and MSK’s Enrico Velardi, a scientist in the van den Brink lab, served as one of the study’s first authors. Jarrod Dudakov, PhD, at the Fred Hutchinson Cancer Center, co-led the study.

Findings:  Researchers found that thymic endothelial cells, which line the blood vessels of the organ, are resistant to damage and are responsible for promoting thymic regeneration via their production of a molecule known as BMP4. These studies lay the foundation for the development of novel therapeutic strategies to boost thymic function in patients whose immune system has been decimated due to aging, infection, or cytotoxic cancer treatments.  

Corresponding author comments: “One reason that cancer is a disease of old age could be that the immune system is less able to combat cancer as we get older,” says Dr. van den Brink, Head of the Division of Hematologic Oncology at MSK. And that, he says, “is directly linked with the thymus being less capable of maintaining a diverse T cell repertoire that can recognize cancer cells.”

“So far, the clinical strategies that have been identified using preclinical models have shown limited benefits in patients,” says Enrico Velardi, a scientist in the van den Brink lab and one of the study’s first authors. “We really need novel strategies to enhance thymus function in patients.”

Funding: This study received financial support from the National Institutes of Health, the Lymphoma Foundation, the Susan and Peter Solomon Divisional Genomics Program, Cycle for Survival, the Cuyamaca Foundation, the Bezos Family Foundation, the European Union’s Seventh Framework Programme, the American Society of Hematology, the DKMS Foundation for Giving Life, Boehringer Ingelheim Fonds, the German National Academic Foundation, the Prostate Cancer Foundation, and the IZKF Würzburg. This research was also supported by the Parker Institute for Cancer Immunotherapy at Memorial Sloan Kettering Cancer Center (M.R.M.v.d.B., Co-Director)