IRF4 and neoplasm: In contrast, in the case of Ag-experienced anti-tumor CD8+ T cells, due to the much smaller levels of tumor antigens presented with MHCs in the TME, the strength of the TCR signal in anti-tumor CD8+ T cells may not be enough to activate Blimp-1 and IRF4 species to suppress PD-1 expression (Figures 2, 3).