PD-1 ligation by PD-L1 expressed on tumors cells transduces signaling via the immunoreceptor tyrosine-based inhibitory motif (ITIM) and the immunoreceptor tyrosine-based inhibitor switch motif (ITISM) of the PD-1 cytoplasmic tail, which further inhibits the PI3K/AKT, MAPK/ERK1/2, and/or mTOR, thus suppressing tumor growth (9). This evidence concerns the gene MAPK3 and neoplasm.