Keywords: IL-21; IL-23; pancreatic cancer; natural killer cells; gene therapy P ancreatic cancer is one of the intractable tumors and the prognosis remained unimproved despite recent progress in therapeutic and detection modalities. 1 It often infiltrates into neighboring tissues or vessels at an early stage and recurrence after surgical operation is common; therefore, a novel therapeutic strategy is required. Augmentation of a host immune system is an approach to suppress progression of the tumors and their metastasis, and transfer of cytokine genes into pancreatic cancer has been investigated for its clinical feasibility. 2,3 Cytokines released from T helper type 1 (Th1) cells are in particular effective in shifting immune systems into a Th1-dominant state, which enhances cell-mediated immunity. 4 Two novel cytokines, interleukin (IL)-21 and IL-23, were recently identified 5,6 and their biological properties analyzed in vitro were linked with Th1 functions. IL-21 is secreted primarily from CD4 + T cells and induces proliferation of activated T and natural killer (NK) cells. 5 IL-21 also increases the lytic functions of cytotoxic T and NK cells; 5 thereby, it can enhance antitumor immune responses. The IL-21 receptor complex consists of the common cytokine receptor g chain and IL-21R. 7,8 A recent study of mice lacking IL-21R demonstrated that IL-21 could facilitate the transition from NK cellmediated innate immunity to T cell-mediated adaptive immunity. 9 However, contradictory results were also reported; IL-21 is secreted from Th2 cells and inhibits the development of interferon-g (IFN-g)-producing Th1 cells. 10 IL-23 is composed of the p19 subunit, which is a novel molecule related to the p35 subunit of IL-12, and the p40