Association Of Lymphocyte Subsets With Efficacy And Prognosis Of PD-1 Inhibitors In Advanced Non-small Cell Lung Carcinoma

Objective:PD-1 inhibitors have achieved significant efficacy in non-small cell lung cancer.However,not all NSCLC patients can benefit from it,so it is necessary to explore biomarkers that can predict the efficacy of PD-1 inhibitors.The purpose of this study was to investigate the differences in peripheral blood lymphocyte subsets in patients with advanced non-small cell lung cancer with different clinicopathological characteristics,to monitor the changes in the proportion of lymphocyte subsets in different efficacy groups before and after immunotherapy,and to analyze the value of lymphocyte subsets in predicting the efficacy and prognosis of immunotherapy.Methods:A total of 153 patients with advanced NSCLC treated with PD-1 inhibitors were included.Gender,age,smoking,pathological type,stage,distant metastasis,the treatment regimen,the number of treatment lines,and PD-L1 expression level were retrospectively collected.Peripheral blood lymphocyte subsets,including CD4~+T cells,CD8~+T cells,CD4~+/CD8~+,NK cells,Tregs,and B cells,were collected by flow cytometry before the first diagnosis,before immunotherapy,and after 4 cycles of immunotherapy.The t-test was used to analyze the differences of lymphocyte subsets before the first diagnosis in patients with different clinicopathological characteristics,and paired t-test was used to analyze the changes of lymphocyte subsets in different efficacy groups before and after immunotherapy.The t-test andtest were used to compare the difference in efficacy between different groups.Logistic regression analysis to determine independent predictors of efficacy in NSCLC patients.Kaplan-Meier curves were drawn,and the differences in PFS between different lymphocyte subgroups were compared using Log Rank test.Cox proportional hazard regression model was used to analyze the independent predictors of PFS when calibrating other variables.Results:1.A total of 153 patients with advanced NSCLC who received PD-1 inhibitors were included,of which 125 patients were tested for PD-L1 expression levels.2.Analysis of lymphocyte subsets in 153 patients before their first diagnosis showed that males had a higher proportion of NK cells than females.The proportion of CD4~+T cells and CD4~+/CD8~+in patients aged≥65 years were lower than those in patients aged<65 years.The CD8~+T cells in peripheral blood of adenocarcinoma patients were higher than those of squamous cell carcinoma patients.There was no significant difference in the proportion of peripheral blood lymphocyte subsets in advanced NSCLC patients with different smoking status,different distant metastases and PD-L1 expression levels.3.After four cycles of immunotherapy,117 patients were classified as the effective group and 36 patients were classified as the ineffective group.The proportions of CD4~+T cells,CD4~+/CD8~+,NK cells and Tregs in the peripheral blood of the patients in the effective group were significantly higher than those before treatment,while the proportion of CD8~+T cells were significantly lower,and there was no significant change in B cells before and after treatment.There was no significant difference in the proportion of lymphocyte subsets before and after treatment in the ineffective group.4.In 125 patients who received immunotherapy and detected the expression levels of PD-L1,PD-L1 expression levels,CD4~+T cells,NK cells and Tregs before immunotherapy were independent predictors of immunotherapy efficacy.5.The median PFS of the 125 patients was 9 months,and PD-L1 expression levels,CD4~+T cells,and NK cells were independent predictors of PFS.Conclusion:There were differences in the proportion of peripheral blood lymphocyte subsets in patients with different gender,age and pathology.PD-1 inhibitors induced changes in the proportion of peripheral blood lymphocyte subsets in patients that responded well to immunotherapy.The level of lymphocyte subsets before immunotherapy has a good predictive value for the efficacy and PFS of patients with advanced NSCLC.