CD8A and cancer: At a higher level, the overall balance between NFAT and CD28/AP-1 activity upon original and/or continued antigen encounter may be critical as anergic CD8+ T cells and CD8+ T cells primed in the absence of CD4+ T cell help or co-stimulation mirror many of the major transcriptional and epigenetic events that occur in PD-1lo/hiCD8+ Tex in both chronic viral infection and cancer (19, 20, 26, 66, 74–80).