PDCD1 and neoplasm: In contrast, engagement of the high-affinity trimeric IL-2R, particularly in combination with PD-1 blockade, has been shown to induce potent therapeutic effects, highlighting the importance of selectively activating cells with high levels of CD25 for successful immunotherapy.22 23 34 However, selective targeting of CD25 on tumor-specific T cells, which transiently upregulate this receptor on antigen recognition, remains a major challenge, as CD25-biased IL-2 agonists inevitably also stimulate Tregs, which constitutively express high levels of CD25.