Abstract C123: Alloferon inhibits migration of pancreatic cancer by regulating the expression of IL-22Rα

Abstract

Abstract Pancreatic cancer frequently metastasizes into one or more organs and tissues located near the pancreas. Metastasis contributes to make curative approach unachievable and bring poor prognosis. Therefore, it is important to develop a strategy to regulate the metastasis of pancreatic cancer. Recent research has reported that IL-22 increases the factors involved in migration and invasion to support the development of pancreatic cancer. The binding of IL-22 to IL-22 receptor exerts its biological effects and, IL-22 receptors are heterodimer receptor complex composed of IL-22Rα and IL-10Rβ. Previously we showed that alloferon, known as the immune modulator, increases chemosensitivity in pancreatic cancer by downregulating the SLC6A14, a transporter of glutamine. In this study, we identified that alloferon is a potential adjuvant therapeutic agent for pancreatic cancer by regulating the expression of IL-22Rα. We found that IL-22 has essential role in migration and invasion of pancreatic cancer by increasing the chemokine receptors such as CXCR3 and CXCR4. In addition, alloferon decreased the expression of IL-22Rα in pancreatic cancer cell line. Therefore, the expression of CXCR3 and CXCR4 decreased in AsPC-1 in presence of alloferon even upon the treatment with recombinant IL-22. To evaluate the effect of alloferon on tumor migration, the migration and invasive capacity were measured in pancreatic cancer cells in absent or present of alloferon. It was observed that alloferon significantly inhibit the migration of AsPC-1 toward ligand of CXCR3 and CXCR4, CXCL10 and CXCL12. These findings established that the expression of IL-22Rα associated with metastasis is likely related to overexpression of CXCR3 and CXCR4 in pancreatic cancer. Taken together, it is suggested that alloferon could be used as an adjuvant therapy to inhibit the metastasis of pancreatic cancer by regulating the expression of IL-22Rα. Citation Format: Hyejung Jo, Yejin Kim, Seulgi Shin, Jae Seung Kang. Alloferon inhibits migration of pancreatic cancer by regulating the expression of IL-22Rα [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C123.