For instance, induction of immune inhibitory ligands such as PD-L1, LGALS9, and TNFRSF14 may reflect an adaptive negative feedback mechanism involving sustained IFNγ signaling (rather than loss of IFNγ activity)25 while CD8 T cell exclusion from the tumor microenvironment may be caused by an immunosuppressive tumor cell secretome driven by aberrant ß-catenin, phosphatase and tensin homolog (PTEN) loss, or CDK-cell cycle signaling pathways29–31. Here, PTEN is linked to neoplasm.