Affiliations 1 State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, PR China. 2 Department of Internal Medicine, Central Medical Branch of Chinese PLA General Hospital, Beijing, PR China. 3 Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, PR China. 4 Department of Digestive Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, PR China. 5 School of Software Engineering, Beijing Jiaotong University, Beijing, PR China. 6 Department of Urology, Shandong Provincial Hospital, Shandong First Medical University, Jinan, PR China. 7 Department of Infectious Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, PR China.
CXC chemokine receptor 4 and programmed cell death-ligand 1 are two critical molecules involved in the tumor immune microenvironment. However, the impact of platinum drugs, such as cisplatin, on CXCR4 or PD-L1 expression and the underlying mechanisms in gastric cancer remain unknown. Moreover, the correlation between their expression levels in GC remains elusive. Immunohistochemistry, western blot, and RT-qPCR were performed to determine the expression pattern of CXCR4 and PD-L1 in GC. Clinic...更多
CXC chemokine receptor 4 and programmed cell death-ligand 1 are two critical molecules involved in the tumor immune microenvironment. However, the impact of platinum drugs, such as cisplatin, on CXCR4 or PD-L1 expression and the underlying mechanisms in gastric cancer remain unknown. Moreover, the correlation between their expression levels in GC remains elusive. Immunohistochemistry, western blot, and RT-qPCR were performed to determine the expression pattern of CXCR4 and PD-L1 in GC. Clinical samples, patient-derived xenografts, and cell-derived xenografts were utilized to investigate the effects of platinum drugs on the expression levels of CXCR4 and PD-L1. Postchemotherapy resected GC tumor tissues showed higher CXCR4 and PD-L1 expression levels than pretreatment biopsies . Similarly, GC xenografts treated with platinum-based chemotherapy exhibited increased CXCR4 and PD-L1 expression levels compared to saline-treated controls . A positive correlation was detected between the expression levels of CXCR4 and PD-L1 in GC tumor tissues. Increased levels of CXCR4 and PD-L1 expression, in a dose- and time-dependent manner upon cisplatin treatment, were observed in GC cells . Cisplatin-induced CXCR4 upregulation relies on ROS/HIF-1α and ROS/NF-κB pathways, while cisplatin-induced PD-L1 upregulation is cyclic GMP-AMP synthase/stimulator of IFN genes-dependent and associated with elevated ROS levels in GC cells. CXCR4 expression was found to be positively correlated with PD-L1 expression in GC. Platinum drugs upregulated the levels of CXCR4 and PD-L1 expression in GC. A combined strategy targeting CXCR-4 and PD-L1 might have clinical prospects for GC patients.收起
发文期刊《Platinum drugs upregulate CXCR4 and PD-L1 expression via ROS-dependent pathways, with implications for novel combined treatment in gastric cancer》历年引证文献趋势图
