Hallmarks of CD8 T cell dysfunction are established within hours of tumor antigen encounter

ATAC-SEQ analysis of antigen-specific CD8 T cells sorted from murine liver tumors and from the spleens of Listeria-infected mice at different early timepoints following adoptive transfer. We sequenced naive antigen-specific CD8 T cells from spleens for comparison. We also sorted tumor-infiltrating antigen-specific CD8 T cells that were removed from tumors and parked in tumor-free hosts for 5 days. The overall goal of this study was to determine the earliest chromatin remodeling events in CD8 T cells activated and differentiating in late tumor-bearing hosts or in infected mice and to determine the extent to which tumor-induced chromatin remodeling was "imprinted." Overall design: CD8+CD90.1+ TAG-specific T cells were (1) sorted from murine liver tumors (TAG-expressing tumors) at 6, 12, and 24 hours and 5 and 10 days of exposure or (2) sorted from B6 mice spleens that had previously been adoptively transferred with tumor-exposed TAG-specific T cells removed from tumors after 24 hours, 5 days, and 10 days or (3) sorted from spleens of Listeria-TAG infected mice at 6, 12, and 24 hours of antigen exposure or (4) sorted from spleens of transgenic TCRTAG mice and ATAC-SEQ was performed.