Overexpressed HAT1 Regulates Cancer Immunity By Increasing PD-L1 Expression In Pancreatic Cancer

Objective Pancreatic cancer is a devastating disease which has an extremely low survival rate.Immunological checkpoint blocking therapy including anti-PD-1(anti-Programmed Death-1)and anti-PD-L1(anti-Programmed Death-Ligand 1)is a new cancer treatment strategy,but the use of PD-L1 inhibitor alone for pancreatic cancer is almost ineffective.Exploring the potential regulatory mechanism of PD-L1 in tumor cells,especially pancreatic cancer cells,is an important strategy to improve the therapeutic effect of PD-L1 blocking for pancreatic cancer.Histone acetyltransferase 1(HAT1)is a type B histone acetyltransferase whose biological role in pancreatic cancer is undefined.This study tried to explore the relationship between HAT1 and PD-L1 and further elucidate its role in pancreatic cancer immunity.Methods We used The Cancer Genome Atlas(TCGA)public database visualization website Gene Expression Profiling Interactive Analysis(GEPIA)to detect the clinical relevance of HAT1 in pancreatic cancer.Western blot and immunohistochemistry were performed on pancreatic cancer tissue microarray slides.Tumor cell viability was explored by colony formation and xenograft experiments.We used Western blot,RT-q PCR and immunohistochemistry to detect the relationship between HAT1 and PD-L1.Results 1.Overexpressed HAT1 is significantly associated with poor prognosis in patients with pancreatic cancer;2.Knockdown HAT1 can decrease the proliferation of pancreatic cancer cells by in vivo and in vitro experiments;3.HAT1 can regulate PD-L1 expression in pancreatic cancer.Knockdown HAT1 can improve the therapeutic effect of immune checkpoint blockade by reducing PD-L1 expression.Conclusion HAT1 can regulate pancreatic cancer cells proliferation and tumor immune response.The discovery of the HAT1 function provides us with new ideas for exploring new treatment methods to overcome the immune evasion of pancreatic cancer cells.