Here, we analysed the PD-1/PD-Ls circuit in TC showing that: i) TC cell lines and TC human samples express, besides PD-Ls, as already demonstrated [16–18], also PD-1 in epithelial cells, whose levels correlated with tumour aggressiveness; ii) intrinsic PD-1 sustains proliferation and migration of TC cells through a SHP2/Ras/MAPK signalling cascade; iii) PD-1 overexpression promotes, while PD-1 blockade inhibits, ATC xenograft growth by affecting cancer cell proliferation. Here, PTPN11 is linked to neoplasm.