It is further essential to distinguish between progenitor exhausted T cells, which express the TF TCF1 and the TCF1−/Tim-3+ terminally exhausted T cells, which co-express the TF TOX, vital for their persistence in the tumor environment with chronic antigen stimulation, with the later population not being re-invigoratable, thus not responding to checkpoint blockade (352, 353, 371). Here, TF is linked to neoplasm.