The effector phase of the anti-tumor immune response induced by anti-PD1 (αPD1) ICB is dependent on cytotoxic CD8+ T cells recognizing tumor cells expressing peptide–MHC class I complexes.12 Surprisingly, the main target on PD1 receptor engagement has been shown not to be the T-cell receptor but instead CD28 co-stimulatory receptor.13 14 PD1 recruits SHP2, which in turn dephosphorylates CD28, preventing tumor-infiltrating lymphocyte (TIL) activation. The gene discussed is PTPN11; the disease is neoplasm.