We're excited to announce our next seminar. Dr. Lamarche will be presenting on Monday June 5th at noon. For Zoom details, please email us at: email@example.com
Caroline Lamarche, MD, MSc
Assistant Clinical Professor
Université de Montréal
“Treg dysfunction and its implication for cell therapy“
Regulatory T cell (Treg) therapy is a promising approach to improve outcomes in transplantation and autoimmunity. It is currently being tested in multiple phase I and II clinical trials in transplantation and autoimmune diseases. We have learned from the work done on conventional T cells that distinct mechanistic states can define their dysfunctions, such as exhaustion, senescence and anergy. All three can negatively impact the therapeutic effectiveness of T-cell based therapies. Whether or not Tregs are also susceptible to exhaustion, and if so, if this would limit their therapeutic effect, was unknown. To "benchmark" exhaustion in human Tregs, we used a method known to induce exhaustion in conventional T cells: expression of a tonic-signaling chimeric antigen receptor (TS-CAR). We found that TS-CAR-expressing Tregs rapidly acquired a phenotype that resembled exhaustion and had major changes in their transcriptome, metabolism, epigenome and function. The finding that human Tregs are susceptible to chronic stimulation-driven dysfunction has important implications for the design of CAR Treg adoptive immunotherapy strategies.
Host: Pierre Olivier-Gaudreau, MD, PhD, MPs, FRCPC