Systemic Immune Inflammatory Index And Lymphocyte Subsets For Immunotherapy And Prognosis Of Lung Cancer

Objective:The efficacy and prognosis of immunotherapy for lung cancer are closely related to the quality and survival of lung cancer patients.The aim of this study was to investigate the relationship between systemic immunoinflammatory indices and lymphocyte subsets on the efficacy and prognosis of immunotherapy for lung cancer,so as to identify more convenient and rapid biomarkers for screening the potential beneficiaries of immunotherapy.Materials and methods:This study included 144 lung cancer patients who applied at least 4 consecutive cycles of PD-1/PD-L1 immunotherapy between January 2019 and October 2022 at the First Hospital of Jilin University.The general information of these 144 patients,such as gender,age,smoking history,BMI,surgery or not,pathological type,clinical stage,whether combined chemotherapy or not,whether first-line immunotherapy was applied,was collected,and the patients’ treatment was followed up to record the treatment protocol,treatment efficacy and progression Free Survival(PFS).Statistical analysis was performed using SPSS 26.0,and statistical differences were considered when P<0.05.First,for continuous variables,normality was tested using the Shapiro-Wilk test.Continuous variables that conformed to a normal distribution were expressed as mean ± standard deviation(x ± S);continuous variables that did not conform to a normal distribution were described by median and interquartile spacing [M(Q1,Q3)].Qualitative information is expressed as number of cases(percentage)(%).Differences in blood count and SII(neutrophil count x platelet count/lymphocyte count)and lymphocyte subsets before and after the first treatment and after 4 cycles of treatment were analysed using independent samples t-test and Mann-Whitney U-test,and the amount of change in SII and lymphocyte subsets before and after immunotherapy was analysed by paired t-test in relation to efficacy.The clinical indicators were statistically analysed using one-way Cox regression analysis,and independent variables with P values <0.05 in the one-way COX regression analysis were included in the multi-way COX regression analysis.Independent predictors of PFS when corrected for other variables were analysed by using Cox proportional risk regression models.KaplanMeier survival curves were also plotted to compare the differences in PFS between different lymphocyte subgroups.Results:1.In the assessment of immunotherapy efficacy,more patients were staged as nonadvanced in the objective remission group than in the non-objective remission group;and more patients were treated with first-line immunotherapy in the objective remission group than in the non-objective remission group(p < 0.05).2.In the assessment of the efficacy of immunotherapy,the objective remission group had higher levels of neutrophil count,lymphocyte count,platelet count and SII count before immunotherapy than the non-objective remission group,with a statistically significant difference in platelets(p=0.003).In both the objective remission group and the non-objective remission group,neutrophil count,lymphocyte count,platelet count and SII count levels decreased after 4 courses of immunotherapy compared to pre-treatment,with a statistically significant amount of change in neutrophils,platelets,lymphocytes and SII in both groups(p<0.001).The objective remission group had higher median CD3+%,CD4+%,NK%,B%,CD4+/CD8+ levels and lower median CD8+% levels after 4 courses of treatment than the non-objective remission group.In both the objective remission and non-objective remission groups,median CD3+%,CD8+%,CD4+% and NK% levels increased after 4 courses of treatment compared to pre-treatment,while median B % and CD4+/CD8+ levels decreased compared to pre-treatment;where the amount of change in CD3+%,CD4+%,CD8+% and B % was statistically different between the two groups(p < 0.05).The objective remission group had higher absolute levels of median CD3+,CD4+,CD8+,NK cells and B cells before treatment than the non-objective remission group.In both the objective remission group and the non-objective remission group,median CD3+,CD4+,CD8+,NK cells and B cells decreased in absolute values after 4 courses of treatment compared to the pre-treatment levels;the amount of change in the above data was statistically different(p < 0.05).3.In the analysis of the correlation between the prognosis of immunotherapy and PFS,clinicopathological characteristics such as gender,pathological type and stage,and whether immunotherapy was applied in the first line were not statistically significant for the prognosis of PFS.In the peripheral blood and SII analysis,in the oneway COX analysis,peripheral blood neutrophils and the amount of change and lymphocyte change after 4 courses of treatment were correlated with the patients’ PFS(p < 0.05).In the analysis of absolute lymphocyte subpopulations and prognostic PFS,in the univariate COX analysis,pre-treatment NK cells,the amount of NK cell change,CD8+ and CD8+ change after 4 courses of treatment,and CD4+/CD8+ and CD4+/CD8+ change after 4 courses of treatment were associated with PFS(P < 0.05).Inclusion of peripheral blood neutrophils and amount of change after 4 courses of treatment,amount of change in lymphocytes,pre-treatment NK cells,amount of change in NK cells,CD8+ after 4 courses of treatment,amount of change in CD8+,CD8+,CD4+/CD8+ and CD4+/CD8+ after 4 courses of treatment in a multifactorial COX analysis showed that: neutrophils after 4 courses of treatment with CD4+/CD8+,and Higher absolute NK cell values before treatment and lower absolute neutrophil values after 4 courses of treatment were associated with better PFS,as were higher CD4+/CD8+ after treatment.4.In the analysis of the correlation between lymphocyte subpopulation percentages and prognostic PFS,CD3+% cells versus NK cells% before treatment and CD4+% versus CD8+% after 4 courses of treatment were associated with PFS in lung cancer immunotherapy patients in a one-way COX analysis(p < 0.05),and for CD3+%cells versus NK% before treatment and CD4+% after 4 courses of treatment versus CD8+% was tested in a multifactorial COX model,showing that CD3+% cells before treatment and CD4+% vs CD8+% after 4 courses of treatment were independent predictors of PFS,all with P values <0.001.lower CD3+% cells before treatment,higher CD4+% after 4 courses of treatment and higher CD8+% after 4 courses of treatment were associated with better PFS.Conclusions.1.the correlation between the efficacy of the objective remission group and the non-objective remission group was assessed: more patients in the objective remission group than in the non-objective remission group were staged as non-advanced(before stage IIIA)and had first-line application of immunotherapy;platelet levels were higher before immunotherapy.2.Prognostic assessment of lung cancer patients: higher absolute NK cell values before treatment,lower absolute neutrophil values after 4 courses of treatment and higher CD4+/CD8+ after treatment were independent risk factors for PFS.Lower CD3+%cells before treatment,higher CD4+% after 4 courses of treatment and lower CD8+%after 4 courses of treatment were independent risk factors for PFS.