PDCD1 and neoplasm: Dimeric PD-1 activates SHP2-mediated immunosuppression by binding to SH2 domains of SHP2 (N-SH2 and C-SH2) via the C-terminal tyrosine-based switch motif (ITSM) of immune receptor (Okazaki et al., 2001; Sheppard et al., 2004; Yokosuka et al., 2012), thus promoting the immune escape of tumor cells.