PD-L1/p-STAT3 Promotes The Progression Of Lung Adenocarcinoma Cells By Regulates TAM Polarization

Objective : The study investigates the mechanism,that PD-L1 regulated Tumorassociated macrophages(TAMs)polarization in tumor microenvironment,which promote malignant progression of lung adenocarcinoma cells,in order to provide a new theoretical basis for the targeted therapy PD-L1 of lung adenocarcinoma.Materials and Methods: 1.The effect of lung adenocarcinoma on TAMs polarization and the ability of α PD-L1 to reverse TAM/M2 polarization were detected by Flow cytometry and ELISA assay after establishing the cells co-culture system.2.Conditioned medium was obtained by IL-13 and α PD-L1 dealing with RAW264.7cells.3.The proliferative ability of lung adenocarcinoma cells was detected by MTT and Clone formation assay after treating with conditioned medium.4.Apoptosis ability of lung adenocarcinoma cells was detected by Flow cytometry after disposing conditioned medium.5.The migration and invasion abilities of lung adenocarcinoma cells treated with conditioned medium or co-culture system were detected by Wound scratch and Transwell assay.6.The effect of α PD-L1 on the lung adenocarcinoma angiogenesis was analyzed through Western Blot and endothelial cell tube formation assay.7.The effect of αPD-L1 on EMT process of lung adenocarcinoma was tested by Western Blot and Immunofluorescence.8.The expression of signaling pathway markers related to αPD-L1 reversing TAM/M2 polarization were detected by Western Blot.Results: 1.Lung adenocarcinoma cells induced the TAM/M2 polarization,which could be reversed by α PD-L1.Lung adenocarcinoma cells and α PD-L1 had no obvious effect on the phenotype change of TAM/M1.2.α PD-L1 could reverse TAM/M2 polarization,but failed to influence proliferation and apoptosis capacities of lung adenocarcinoma cells.3.α PD-L1 slowed down the migration and invasion of lung adenocarcinoma cells induced by TAM/M2 polarization significantly.4.αPD-L1 restrained lung adenocarcinoma angiogenesis through reversing TAM/M2 polarization.5.α PD-L1 inhibited EMT process of lung adenocarcinoma cells by reversing TAM/M2 polarization.6.αPD-L1,suppressing STAT3 phosphorylation significantly in TAM/M2 of Co-culture system,reversed TAM/M2 polarization process.Conclusions: α PD-L1 reversed TAM/M2 polarization by suppressing STAT3 phosphorylation in TAM/M2 so as to inhibit lung adenocarcinoma cells migration,invasion,angiogenesis and EMT process.However,α PD-L1 had no effect on proliferation and apoptosis abilities of lung adenocarcinoma cells.