Study On The Interaction Of Reducing T Cell Activity By Reactive Oxygen Species In Non-small Cell Lung Cancer

Objective:Primary bronchogenic carcinoma(Abbreviated lung cancer)is a very common malignant tumor nowadays.It has aroused more attention of the medical community and patients for non-small cell lung cancer(NSCLC)that occupies about 80%-85% of the pathological types.Related studies have confirmed that the growth of tumor cells is closely related to the immune effect of T cells in the tumor microenvironment(TME),and further related studies have shown that reactive oxygen species(ROS)such signaling small molecules have a wide range of effects on the differentiation and maturation,activation,migration,metabolism and death of T lymphocytes.The aim of this study was to investigate the ROS content in cultured T cells from tumor tissues of patients with non-small cell lung cancer(NSCLC)and peripheral blood T cells of healthy normal subjects,and to detect the signal intensity of T cell receptors,so as to analyze the effect of anti-tumor effect of corresponding T cells and explore the related role of ROS in T cell anti-tumor,so as to provide a feasible reference for future immunotherapy of NSCLC.Methods:In this study,we collected tumor samples from patients who underwent surgery in the Department of Thoracic Surgery of China-Japan Union Hospital of Jilin University from September2020 to September 2021 and peripheral blood T cells from normal healthy people,cultured the two,and further used NSCLC cell line A549 and peripheral blood T cells from healthy people to establish a NSCLC-T cell co-culture platform.A549 cells were treated with non-small cell lung cancer plasma and stimulated with anti-CD3/CD28 beads,and ZAP70 phosphorylation levels were detected by flow cytometry with specific reagents.ZAP70 phosphorylation levels were also measured in peripheral blood T cells from normal healthy people after incubation with A549 cells and stimulation with anti-CD3/CD28 beads.Tumor tissue T cells from NSCLC patients with high ROS content and low ROS content tumor cells were again stimulated with anti-CD3/CD28 beads to detect ZAP70 phosphorylation levels.Results:Through multiple comparison experiments,it was found that the phosphorylation level of ZAP70 in A549 cells treated with peripheral blood T cells from normal healthy people was significantly higher than that in A549 cells treated with plasma from NSCLC patients under the same conditions.However,for the ROS experimental group,the ZAP70 phosphorylation level in the high ROS content group was significantly lower than that in the low ROS content group.Conclusion:Current studies have shown that the generation,development,invasion and metastasis of tumors are not caused by a single factor,but involve the results of many different factors,and the available evidence shows that the imbalance of immune surveillance and immune tolerance is the basic factor of tumor formation.With the researchers’ deep understanding of the mechanism of tumor immune escape,the formation of tumors is closely related to the tumor immune microenvironment.The tumor microenvironment affects the escape of tumor cellular immunity,and then has a certain impact on the prognosis of patients,so it is particularly important to study the cellular immunity that plays a major role in tumors in the immune system,especially the study of T cells.According to current known experimental studies,apoptosis and necrosis of T cells are inextricably related to ROS.Many different sources of ROS are involved in this process in T cell activation-induced cell death(AICD).Activation of T cell receptor(TCR)promotes the development of AICD.In this study,TCR signal intensity(ZAP70phosphorylation level)was used to observe the activation and function of T cells.It was found that the high ROS level of NSCLC cells predicted the defect of TCR signal of T cells in tumor tissues,which would lead to the weakening of cellular immune function of T cells to tumor cells and facilitate the growth and metastasis of tumor cells.In addition,the relevant TCR signal intensity(ZAP70 phosphorylation level)of healthy people and NSCLC patients in this study could also observe that NSCLC inhibited the activation of T cells.Based on the consideration of the above views,the study of the effect of reactive oxygen species on mediating non-small cell lung cancer by regulating T cells is helpful to provide a favorable reference for future immunotherapy and provide a more meaningful further research direction for scientific research work.