1. Scientific Committee on Transplantation Biology and Cellular Therapies
Targeting T cell exhaustion
Nick Haining, B.M., B.Ch.
Dana-Farber Cancer Institute
Harvard Medical School
Broad Institute of Harvard and MIT
2. T cell exhaustion
Memory T cells
Acute infection, vaccination
Can respond to restimulation
Persist without antigen
Exhausted T cells
Chronic infection, cancer
Spectrum of functional defects
Require antigen for persistence
4. Exhausted T cells have heterogeneous fates and functions
Progenitor
Residual proliferative capacity
Retained cytokine production
Reinvigoration potential
Terminal
Cytotoxic capacity
Localization to tissues
More inhibitory receptor expression
Exhausted T cells
5. Open questions
• How do inhibitory receptors shape the immune response in health and
disease?
• What is the optimal way to block inhibitory receptors to engage
therapeutic tumor immunity?
• How can effective immunotherapy combinations be rationally identified?
• What are the drivers and regulators of inhibitory receptor expression?
• What roles do different exhausted T cell subsets play in the response to
cancer?
Recent work has shown these two states differ not only functionally but also in their program of gene expression and in the fundemental regulatory programs encoded by their epigenetic landscape – separate cell state
Checkpoint blockade reinvigorates the function of exhausted cells…but this reinvigoration is at the population level
