Study On The Relationship Between Lymphocyte Subsets And Cytokines And Therapeutic Efficacy Of Advanced Non-small Cell Lung Cancer

Background and Purpose:Lung cancer is one of the most common malignancies,with non-small cell lung cancer(non-small cell lung cancer,NSCLC)accounting for the vast majority.Most patients progress to advanced stages when diagnosed,so the overall survival rate of lung cancer patients is low.However,new treatments for advanced NSCLC are emerging,the most prominent of which is targeted therapy for lung cancer driver gene positivity,while negative patients mainly rely on systemic chemotherapy,and the therapeutic efficacy is limited.At present,the emergence of immunotherapy has significantly changed the treatment mode of advanced NSCLC,especially for patients with driving genes negative,which brings more hope of survival.At present,a number of clinical studies at home and abroad have confirmed programmed death-1(programmed death-1,PD-1)/programmed death protein ligand-1(programmed death-ligand 1,PD-L1)inhibitors are effective in the treatment of non-small cell lung cancer and have long-lasting antitumor effects,it results in a longer progression-free survival(progression-free survival,PFS)and overall survival(overall survival,OS)for lung cancer patients.Studies of the mechanism of action of immune checkpoint inhibitors(immune checkpoint inhibitors,ICIs)have been found to block PD-1/PD-L1 Signaling pathways to induce the proliferation of T lymphocytes and enhance their activity,improve the tumor immune microenvironment and thus play a role in inhibiting or killing tumor cells.Lymphocyte subsets and cytokines are important members of immune microenvironment.In this study,the changes of lymphocyte subsets and cytokines in patients before and after immunotherapy were observed to find the relationship between them and curative effect.Methods:Through the electronic medical record system of Henan Province People’s Hospital,the hospital was searched and collected from January 2020 to June 2021 Patients with advanced NSCLC diagnosed and treated with diagnosis.The patients who underwent at least 4 consecutive cycles of immunotherapy were screened and collected.Fasting peripheral blood was extracted from these patients 1 day before the first immunotherapy and 20 days after 4 cycles of immunotherapy,and the levels of cytokines and lymphocyte subsets were tested by flow cytometry and the numerical changes were recorded and analyzed.Moreover,imaging examinations were performed every 2 cycles to evaluate the efficacy of tumors according to response evaluation criteria in solid tumors(response evaluation criteria in solid tumors,RECIST).A total of 52patients were collected according to the above screening criteria.After 4 cycles according to different efficacy(complete response CR;partial response PR;stable disease SD;progressive disease PD)divides it into control groups(CR+PR+SD)and invalid groups(PD).The changes in lymphocyte subset levels between and within the two groups before and after treatment,and the relationship between lymphocyte subsets and cytokine levels and efficacy were compared.Follow-up of these 52 patients was recorded until disease progression or death.SPSS21.0 software was used for statistical analysis.Measurement data for normality and variance homogeneity test,if the measurement data is in line with the normal distribution,using(x±s)indication,before and after treatment between the two groups using independent sample t test,non-normal distribution of intergroup and intra-group treatment before and after comparison using non-parametric test Mann-Whitney U test,expressed in median(quartile)spacing,counting data group x~2 test,Cox regression model for one-way analysis,Pearson correlation was used to analyze the association between lymphocyte subsets and cytokines and efficacy,and Kaplan-Meier was used in survival analysis without progression.P<0.05for the difference was statistically significant.Results:1.The level of B lymphocytes before treatment in the control group was significantly higher than that in the ineffective group,which were 139[98.5,199.5](/μL)and 96.2[55.7,127.7](/μL)respectively,P=0.043.2.Except for B lymphocytes,the level of the remaining lymphocyte subsets was not statistically significant before immunotherapy in different therapeutic groups(P>0.05).3.The proportion of CD3~+CD4~+lymphocytes,lymphocyte count level,total T lymphocyte count level and CD4~+T lymphocyte count in the control group after the 4 cycle of immunotherapy were significantly higher than those in the ineffective group,respectively 36.87±11.54(%)and 28.09±10.34(%);1615.05±565.49(/μL)and 1158.25±546.97(/μL);1099.03±389.63(/μL)and 747.08±403.02(/μL);572.03±249.42(/μL)and 347.85±234.08(/μL)(P-value is average<0.05).4.Cox univariate analysis showed that the effect of before treatment B lymphocyte level on tumor efficacy showed that HR(95%CI)was 0.987(0.975,1.000),and P=0.049.5.After treatment CD3~+CD4~+proportion of lymphocytes,lymphocyte count level,total T lymphocyte count level and CD4~+T cell count level there is a significant inverse association with tumor progression(r-value mean<0,P<0.05),and the higher the expression level,the more energy it can be acquire longer PFS.6.The high expression of IL-4 and IL-6 in cytokines was positively correlated with tumor progression(r-values were 0.597 and 0.577,respectively,and P was less than 0.05),and the higher the expression,the shorter the PFS.Conclusion:In patients with advanced NSCLC,the level of B lymphocytes in the control group before treatment was significantly higher than that in the ineffective group,and its count level could be used as a protective factor affecting tumor efficacy,reflecting that the level of B lymphocytes may have a certain predictive role in the evaluation of therapeutic efficacy.After continuous immunotherapy,the level of some T lymphocyte subsets in the control group was significantly higher than that of the ineffective group,suggesting that after continuous immunotherapy,patients with tumor control could obtain better T cell immunity than patients with progression,and T lymphocyte levels were positively correlated with PFS,IL-4 and IL-6 levels were inversely correlated with PFS.This change in immune cell level and its relationship with the efficacy reflects that lymphocyte subsets and cytokines have certain reference value for the evaluation of treatment effect in the process of immunotherapy.