Conversely, the Treg generation induced by the IL-21low/PD-L1low tumor explants failed to be reversed by neutralizing IL-21 (24.4 ± 3.7% vs. 25.8 ± 2.4%, P > 0.05), PD-1 (22.8 ± 2.4% vs. 25.8 ± 2.4%, P > 0.05), or both IL-21 and PD-1 (22.5 ± 3.1% vs. 25.8 ± 2.4%, P > 0.05), indicating that Treg generation in the IL-21high/PD-L1high tumor microenvironment may be regulated by mechanisms distinct from those in the IL-21low/PD-L1low tumor microenvironment (Figures 5A, B). This evidence concerns the gene IL21 and neoplasm.