Gene expression comparison of exhausted CD8 T cells that respond or do not respond to PD-1 blockade

CD8 T cells that respond to PD-1 blockade (during the early stage of infection) have enriched CD28 costimulation genes During the early stages of chronic infection PD-1 blockade is effective are rescuing exhausted CD8 T cells. However during the later stages of chronic infection PD-1 blockade is not able to induce a significant rescue of exhausted T cells. In order to understand the transcriptional basis of these difference we performed an RNA comparison. There is enrichment in several genes and pathways, and we hypothesize that these could be exploited for optimizing immune checkpoint therapies during the later stages of chronic infection. We FACS-sorted exhausted CD8 T cells from chronically infected mice (lifelong model of LCMV Cl-13 infection) at 2 different times when PD-1 blockade is effective or when PD-1 blockade is not effective