Effect Of Mesenchymal Stem Cells On PD-L1 Expression In Non-small Cell Lung Cancer

Lung cancer is the leading cause of cancer death worldwide.In clinic,lung cancer is categorized into small cell lung cancer(SCLC)and non-small cell lung cancer(NSCLC),and about 80%-85% of patients suffer from NSCLC.Because lung cancer is asymptomatic at the early stages,about 75% of patients with NSCLC are already in the middle and advanced stages at the time of diagnosis,of which have missed the best period for surgical treatment.At present,the main treatment methods of advanced lung cancer are radiotherapy,chemotherapy,molecular targeted therapy,but the outcomes remain less than satisfactory.With the rapid development of tumor immunotherapy in recent years,promising efficacies have been achieved in treating late stage lung cancers.In particular,blockages of programmed cell death 1(PD-1)and programmed cell death-ligand(PD-L1)have been identified as the best treatment for advanced lung cancer.Currently,PD-1/PD-L1 blockers can increase the 5-year survival rate of advanced non-small cell lung cancer from about 5% to 15%.Since binding of PD-1/PD-L1 is blocked by antibodies,the body's own immune system is strengthened,resulting in a series of immune responses that suppress tumor growth and achieve the effectiveness of treating cancer.However,some side effects of this therapy have limited it's applications.Major side effects include arthritis,lupus erythematosus,nervous system and other autoimmune diseases.Since mesenchymal stem cells(MSCs)have the potentials in alleviating body's immune responses,it might be a good therapy to combine the PD-1/PD-L1 blocker treatments with MSCs.MSCs are adult stem cells originating from the mesoderm with the ability of self-renewal and multi-directional differentiation.Currently,they are mainly used in clinical treatment of autoimmune diseases,nervous system diseases,and digestive system diseases.In addition,the efficacy of PD-1/PD-L1 blockers is positively correlated with the expression level of PD-L1 in tumor cells.The higher the expression level of PD-L1,the more significant the effect is.When the patient's tumor tissue does not express PD-L1,the therapy will not be effective.Therefore,this study explored the effect of mesenchymal stem cells on the expression of PD-L1 in non-small cell lung cancer cells,as well as the proliferation,apoptosis,and migration of lung cancer cells.It tested the feasibility of combining MSCs with PD-1/PD-L1 blocker for the treatment of advanced stage of lung cancer.In this study,we used lung cancer cell lines A549 and H1299 to study the effect of mesenchymal stem cells on the PD-L1 expression level and migration ability of lung cancer cells.The research objectives include the following three aspects:(1)Detecting the expression of PD-L1 in the tissues of lung cancer patients by immunohistochemistry;(2)Detecting the effect of hucMSCs on the expression of PD-L1 genes and proteins on A549 and H1299 cells,using qRT-PCR,Western blot and immunity fluorescence techniques;(3)Exploring the effect of MSCs on the functions of A549 and H1299 cells.Transwell invasion and scratch repair experiments were used to detect the homing of MSCs on NSCLC cells.And the effect on the migration of NSCLC cells,and the expression of cell proliferation(Ki-67)and apoptosis(Bax,Bcl)were detected by qRT-PCR experiment.The experimental results indicated that hucMSCs can increase the expression of PD-L1 in NSCLC cells,have homing properties for NSCLC cells,and can inhibit the proliferation of NSCLC cells and promote their apoptosis while also inhibiting the migration of NSCLC cells.This study provided a theoretical basis for finding novel therapies in combine with the PD-1/PD-L1 immunotherapy,which may improve its therapeutic effects on advanced lung cancer with reduced side effects.