CD28 and melanoma: Furthermore, treatment with rapamycin (sirolimus), which specifically blocks MTORC1 signaling during TCR (anti-CD3/CD28) stimulation of melanoma TILs, resulted in consistent downregulation of PD-1 expression, particularly in the CD8+CD45RA− memory T cells and CD8+CD45RA-CCR7−CD27− effector memory T cells in the tumors (Figure 4B).