The dysfunctional or exhausted T-cell state is typically regulated by programmed death (PD)-1/PD-ligand (L)1 signaling, in which PD-1 expressed by the T-cell is bound by PD-L1 present on the mammary tumor cells as well as the MDSCs and macrophages in the TME (40, 41). This evidence concerns the gene CD274 and breast cancer.