Decreased NSG3 enhances PD-L1 expression by Erk1/2 pathway to promote pancreatic cancer progress

Inhibiting the functioning of PD-1/PD-L1 to activate human immune system and improve the prognosis of pancreatic Cancer (PC) would provide a significant boost to handling the disease. One research found the expression level of NSG3 was reduced in pediatric pilocytic astrocytoma, so is PC and we found NSG3 could regulate the expression of PD-L1. So NSG3 could become a new target for enhancing the immune response to PC. The GEPIA website was employed to analyze the prognoses in PC patients with different NSG3 levels. Immunohistochemistry (IHC) analysis was applied to detect different levels of NSG3 in para-PC and PC tissues. Cell biological function tests (in vitro) were performed and a subcutaneous nude mice tumor model (in vivo) was established to verify the effect of NSG3 on PC. Immunoblotting and RT-qPCR were utilized to demonstrate the inhibiting effect of NSG3 on PD-L1 through regulating ERK1/2 phosphorylation. A subcutaneous C57BL/6 tumor mice model was established to assess the possibility of a synergistic effect of NSG3 expression and the use of an anti-PD-L1 antibody on PC. PC tissues had decreased NSG3 expression levels, which led to poor prognosis. Overexpressing NSG3 suppressed proliferation, invasion and migration capacities of PC cells. On the contrary, knocking-down NSG3 prompted PC malignancy whether in vivo or in vitro. Importantly, NSG3 prevented ERK1/2 phosphorylation to inhibit PD-L1 expression. Additionally, NSG3 and an immune checkpoint inhibitor anti-PD-1 antibody acted synergistically, which enhanced the efficacy of the inhibitor. NSG3 inhibited PD-L1 expression by suppressing ERK1/2 phosphorylation to improve the immune response to PC. NSG3 is, therefore, a potential new diagnostic and prognostic marker, particularly useful in immune checkpoint blockade therapy.