Antitumor activity of IL-21 in mantle cell lymphoma. The main (A) direct and (B) indirect effects are shown. Direct effect: IL-21 receptor engagement leads to activation of the intrinsic apoptotic pathway in neoplastic cells in a STAT3- and MYC-dependent manner. Indirect effects: IL-21 increases NK and CD4⁺ T-cell activity in the tumor microenvironment and leads to enhanced lysis of tumor cells.