We have identified altered cellular metabolism as a fundamental driver of T-cell exhaustion (Vardhana et al, Nat Immunol 2020). We now aim to understand the specific mechanisms by which T-cell metabolism becomes altered, and how the resultant metabolic alterations activate the global exhaustion program:
- How do changes in cellular metabolism contribute to the extent to which antigen avidity and dose drive T-cell exhaustion?
- How do changes in cellular metabolism contribute to the extent to which antigen avidity and dose drive T-cell exhaustion?How do changes in cellular metabolism contribute to the extent to which antigen avidity and dose drive T-cell exhaustion?How do changes in cellular metabolism contribute to the extent to which antigen avidity and dose drive T-cell exhaustion?
- What are the epigenetic, post-transcriptional, and post-translational mechanisms by which metabolites activate the T-cell exhaustion program?
- How do exhaustion-associated transcription factors, such as TOX, alter intratumoral T-cell metabolism?