IL-18's immunotherapeutic effect on pancreatic cancer

Purpose:We sought to find new immune-based treatments for pancreatic cancer (PC). Experimental Design: We detected interleukin (IL)-18 expression in plasma and specimens from patients with PC. We then investigated whether IL-18 had a therapeutic effect for PC in vitro and in vivo, and any underlying mechanisms. Results: Higher plasma IL-18 was associated with longer overall survival, but higher IL-18 in PC tissues was associated with shorter overall survival and increased invasion and metastasis. Recombinant IL-18 alone had no antitumor effect in the syngeneic mice with orthotopically transplanted tumors and promoted tumors in immunocompromised mice; it also facilitated immune responses in vitro and in vivo by augmenting the activity of cytotoxic T cells and NK cells in peripheral bloods and lymph nodes. However, IL-18 promoted the proliferation and invasion of PC cells, in vitro and in vivo, through the NF-B pathway. Nevertheless, by co-administrating IL-18 with BAY11-7082, a NF-B inhibitor, we were able to prevent the pro-cancerous effects of IL-18 and prolong the survive time of the mice. Conclusions: IL-18 has both cancer-promoting and cancer-suppressing functions. Although its single-agent treatment has no therapeutic effect on PC, when combined with the NF-B pathway inhibitor, IL-18 improved survival in a murine PC model. Our study implies the possibility of a combinational immunotherapy that uses IL-18 and targets NF-B pathway.

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