Altogether these data suggest that the reduced activation of STAT3/NF-kB observed in cancer cells of IL-21-deficient Apcmin/+ mice is not due to the lack of a direct effect of IL-21 on these cells but probably reflects the diminished synthesis of IL-17A, IL-22, TNF-α and IL-6, given that these cytokines directly activate STAT3 (IL-22 and IL-6) or NF-kB (IL-17A and TNF-α) in malignant cells [19]. This evidence concerns the gene TNF and cancer.