Additional approaches seek to destabilize the suppressive Treg lineage by targeting transcriptional and metabolic pathways, including STAT3 inhibition, COX-2/PGE2 blockade, and disruption of the PD-1–SHP-2 axis, each of which can reduce Treg-mediated suppression in tumor tissues (61, 83, 85). Here, PDCD1 is linked to neoplasm.