IL-12 can directly downregulate the expression of PD-1 on human TILs. a Tumor cell suspensions from human melanoma tumors were incubated with 10 ng/ml human IL-12 for 72 h, and the expression of PD-1 among CD8+ T cells was determined by flow cytometry before and after culture. (n = 3). b The same tumor cell suspensions were cultured in the presence of anti-CD3/CD28 beads with or without IL-12, and production of IFN-γ among CD8+ T cells was determined by flow cytometry (n = 5). One-tailed paired Student’s t test was used, *p < 0.05, **p < 0.005, and ***p < 0.0001. c Cell suspensions from a B16 melanoma tumor were incubated with 10 ng/ml murine IL-12 for 72 h, and the expression of PD-1 among CD8+ T cells was determined by flow cytometry