New Hope for Repairing a Damaged or Aging Immune System

Three-dimensional reconstruction of the blood vessels in a mouse thymus using light-sheet fluorescent microscopy

This image of a mouse thymus, made using light-sheet fluorescent microscopy, shows the three-dimensional structure of blood vessels in the organ. The thymus plays a primary role in training the immune cells that protect us from disease.

Love your thymus. This small butterfly-shaped organ in the upper chest is where your immune system’s T cells develop. The training these cells receive in the thymus equips them for a life of fighting off infections and diseases, like cancer.

As we age, thymus function declines, and so does the ability of our immune system to combat its foes.

“Once you get to be 50 or 60 years old, your T cell repertoire is greatly limited compared with what it used to be when you were in your teens and 20s,” says Memorial Sloan Kettering physician-scientist Marcel van den Brink. “Simply being able to benefit from a flu shot is compromised in many people over the age of 60.”

Damage to the thymus from certain types of cancer treatment can also impair thymus function, complicating recovery.

A new study from Dr. van den Brink’s lab at MSK — in collaboration with Jarrod Dudakov at the Fred Hutchinson Cancer Research Center — has identified a molecule that promotes thymus regeneration. The results pave the way toward treatments that could one day help rejuvenate an aging or damaged thymus.

A Thymus Repair Molecule

Called BMP4, the molecule is produced by cells that line the blood vessels coursing through the thymus. In mice, the molecule helps the thymus repair itself after an injury, such as radiation exposure, the researchers found. They suspect it does the same in humans and plan to test that next.

Ultimately, their hope is to use BMP4 as a drug. Alternatively, they might be able to deliver cells that secrete BMP4 into the thymus, to repair that organ’s functioning.

According to Enrico Velardi, a scientist in Dr. van den Brink’s lab who is one of the study’s first authors, previous attempts at giving the thymus a boost have been disappointing. “We really need novel strategies to enhance thymus function in people with cancer,” he says.

While preliminary, the study results have broad implications for both cancer treatment and prevention. “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,” Dr. van den Brink notes. 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.”

A study describing these results appears today in Science Immunology.

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 Parker Institute for Cancer Immunotherapy at MSK, 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.