Cluster Seminar by Debattama Sen (Harvard)

June 18, 2019 - June 18, 2019


Dr. Debattama Sen
Haining Lab, Dana-Farber Cancer Institute, Harvard

Epigenetic Determinants of CD8+ T cell Exhaustion

Date and Time
Tuesda, June 18, 2019 at 11:00 a.m

Lecture hall (basement floor)
Biomedizinisches Zentrum (BMZ), Venusberg

Prof. Christian Kurts & Dr. Zeinab Abdullah


T cell exhaustion describes an acquired dysfunction common in settings of chronic viral infection. Despite clinical efforts to rescue exhaustion, the fundamental mechanisms specifying this state, and the potential for reprogramming exhausted T cells, remain poorly understood. Since the epigenome can govern cell state, we profiled accessible chromatin in exhausted CD8+ T cells. Exhausted cells acquired a state-specific landscape of enhancers that profoundly differed from functional memory. Comparison of mouse cells to those isolated from HCV and HIV infection identified a conserved epigenetic program of exhaustion. Critically, CD8+ tumor infiltrating lymphocytes (TILs) also shared epigenetic and transcriptional features with chronic viral infection, suggesting that T cell exhaustion is a fundamental adaptation to settings of chronic stimulation.