can regulatory t cells be modulated to avoid autoimmunity without losing the therapeutic benefit on immune-checkpoint inhibitors?

Dr. Zemmour’s work is focused on regulatory T cells (Treg), which are unique cells that specialize in immunosuppression, preventing autoimmune disease but also promoting cancer growth. In past work, he identifies 11 core genes that appear to regulate Treg function and that might serve as targets in various diseases, allowing both the use of agonists to enhance Tregs to treat autoimmune disease and the use of inhibitors to treat cancers. Now, Dr. Zemmour hopes to understand Treg pathways more clearly, to understand whether the same pathways that allow tumor suppression are also involved in tissue tolerance. Additionally, Tregs are involved in modulating the behavior of other cells, which make them an ideal focus for studying how cells communicate.

As a basis for his study, Dr. Zemmour will consider immune checkpoint inhibitors (ICIs). ICIs are used to treat cancer by activating T cells through the inhibition of immune checkpoint molecules. However, ICIs often trigger autoimmunity issues, with up to 70% of ICI patients developing immune-related adverse effects (irAEs) like colitis. Both the therapeutic benefit and the irAEs are related to Treg activity. Dr. Zemmour will first seek to determine if Tregs are ineffective in preventing ICI colitis because there are changes in the mix and balance of Tregs with different origins, stability, and other intrinsic properties. Next, he hopes to clarify if changes in the crosstalk between Tregs and CD8 T cells allow ICI colitis. Finally, Dr. Zemmour will test if he can create a therapeutic intervention in a mouse model that treats ICI colitis without interrupting its anti-tumor abilities. He hopes to gain a much better understanding of how regulatory T cells behave and influence other cells, and in the process potentially find new ways to alleviate immune-related adverse effects like ICI colitis in cancer patients receiving therapy.