Immunologist and Assistant Professor, Dr. Ann Griffith, has dedicated her research to the study of thymus biology and its effects on the immune system. Initially focusing on health during the aging process, in 2017 she was awarded the Max and Minnie Tomerlin Voelcker Award, allowing her research to expand into cancer therapy. Since receiving the prestigious award, Dr. Griffith has made significant strides. Her Voelcker funded research investigates the long-term effects of cancer therapy on the immune system, as well as new methods to prevent immunodeficiencies caused by treatment.
Dr. Griffith explains, “Cancer patients who undergo radiation and chemotherapy suffer a reduction in the size of their thymus, which is the tissue that produces T cells, and the thymus is particularly slow to recover after cancer therapy. This slow thymus rebound after treatment means that very few new T cells are produced, leaving patients more vulnerable to infection and cancer relapse.”
She goes on to state that it is unclear why the thymus recovers so slowly but believes her research may provide answers to a faster recovery.
“In the last several years, we have found that the rare cells in the thymus that direct T cell development, stromal cells, lack a key antioxidant enzyme, catalase, that is critical for detoxifying reactive oxygen species (ROS). In mice, supplementing antioxidant activity can slow the loss of thymus size that occurs during aging. Since traditional cancer therapies like radiation and chemotherapy create high levels of ROS, it may be the antioxidant deficiency in thymic stromal cells that leaves the thymus so susceptible to damage induced by cancer therapies. If so, antioxidant supplementation during treatment may protect stromal cells in the thymus from damage, allowing better thymus recovery, and therefore better T cell immunity after cancer therapy.”
Dr. Griffith and her team are testing this concept using genetic or dietary antioxidant supplementation in mice. Based on her preliminary data, antioxidant supplementation during radiation and bone marrow transplant results in approximately 2-fold increases in the size of the thymus 8 weeks after transplant. The long-term goal of these experiments is to minimize infection and relapse in patients being treated for cancer.
Even more ground-breaking, Dr. Griffith believes that antioxidant supplementation could improve the efficiency of newly emerging cancer immunotherapies, including checkpoint inhibitor therapies (frequently used simultaneously with or after traditional therapies).
“Checkpoint inhibitors enhance killing of tumor cells by T cells and therefore depend on the presence of T cells bearing T cell receptors that recognize tumor antigens. Since traditional therapies damage the thymus, the number and diversity of T cells is low after treatment. Enhancing thymus recovery after radiation and chemotherapy would expand the diversity and frequency of T cells that may recognize tumor antigens, potentially enhancing the efficacy of subsequent immunotherapies like checkpoint inhibition.”
As Dr. Griffith’s research develops, the implications could have a worldwide impact. The CDC estimates 4,285 cancer patients die due to serious infection in the US alone. Antioxidant supplementation during treatment could be the key to improving cancer therapies and a healthy treatment recovery.
This article was written by Karoline Austin, the Assistant to the Chair in the Department of Microbiology, Immunology & Molecular Genetics.