Combining protein arginine methyltransferase inhibitor and anti-programmed death-ligand-1 inhibits pancreatic cancer progression
Nannan Zheng, Min Zhou, Fang Sun, Manxiu Huai, Yi Zhang, Chun-Ying Qu, Feng Shen, Leiming Xu
Abstract
BACKGROUND: Immunotherapy targeting programmed death-1 (PD-1) or programmed death-ligand-1 (PD-L1) has been shown to be effective in a variety of malignancies but has poor efficacy in pancreatic ductal adenocarcinoma (PDAC). Studies have shown that PD-L1 expression in tumors is an important indicator of the efficacy of immunotherapy. Tumor cells usually evade chemotherapy and host immune surveillance by epigenetic changes. Protein arginine methylation is a common posttranslational modification. Protein arginine methyltransferase (PRMT) 1 is deregulated in a wide variety of cancer types, whose biological role in tumor immunity is undefined. AIM: . METHODS: . By flow cytometry, we determined the expression of key immune checkpoint proteins, detected the apoptosis in tumor tissues, and analyzed the immune cells. Immunohistochemistry staining for cellular proliferation-associated nuclear protein Ki67, TUNEL assay, and PRMT1/PD-L1 immunofluorescence were used to elucidate the underlying molecular mechanism of the antitumor effect. RESULTS: < 0.001) in tumor tissue compared to the control. In addition, PT1001B amplified the inhibitory effect of anti-PD-L1 on tumor cell proliferation and enhanced the induction of tumor cell apoptosis. PRMT1 downregulation was correlated with PD-L1 downregulation. CONCLUSION: PT1001B enhances antitumor immunity and combining it with anti-PD-L1 checkpoint inhibitors provides a potential strategy to overcome anti-PD-L1 resistance in PDAC.