The Study Of IL-36β Expression In Pancreatic Cancer And Its Function On Inhibiting Tumor

Objective:To investigate the expression of IL-36βin tumor tissues and adjacent tissues of pancreatic cancer patients by qPCR and immunohistochemistry.To establish the stable IL-36βhigh expressing pancreatic cancer cell line Panc02 and analyze the anti-tumor role of IL-36βin tumor microenvironment.To observe the in vivo effectiveness on murine pancreatic cancer by intratumoral injection of recombinant adenoviral vector carrying IL-36β.Methods:The pancreatic cancer tissues and adjacent tissues were obtained by surgical removal from clinically confirmed 40 patients with pancreatic cancer.Based on extracting total RNA from pancreatic cancer and adjacent tissues with Trizol,the expression of IL-36βwas detected by the method of RT-qPCR.At the same time,the expression of IL-36βin tumor tissues and paracancerous tissues were verified by immunohistochemistry analysis.Establishing the stable IL-36βhigh expressing pancreatic cancer cell line Panc02 and injecting the cell suspension subcutaneously in mice.The tumor growth was measured every 2 days.The mice were sacrificed when the observation was over and the tumor microenvironment was detected by flow cytometry.The IL-36βadenovirus was injected into the tumor on the 7th day after tumor model was established.The tumor growth was also measured every 2 days and Flow cytometry was used to detect tumor microenvironment.Results:The results showed that expression of IL-36βm RNA in paracancerous tissues was higher than tumor tissues(P<0.05).The immunohistochemistry analysis showed the same result.In vivo,IL-36βsecreted in the tumor microenvironment by Panc02-IL-36βcan significantly inhibit tumor growth and type 1 lymphocytes,such as CD8~+T cells and NK cells were increased.Similarly,intratumoral injection of IL-36βadenovirus can significantly inhibit tumor growth and increase the content of CD8~+T,NK andγδT cells.Conclusion:IL-36βexpression significantly decreased in cancer compared with paracarcinoma,suggesting that IL-36βin the tumor microenvironment possibly effect on anti-tumor response and its downregulation may contribute to tumorigenesis.The transfectant Panc02-IL-36βstably secreting mouse IL-36βhas been established and IL-36βexpressed in the tumor microenvironment can prominently inhibit tumor growth and increase the content of CD8~+T,NK cells.IL-36βadenovirus can be used as a tumor vaccine,and it also can significantly inhibit tumor growth.