Analysis Of Differences In Immune Microenvironment Between Patients With EGFR Mutation And Wild-type NSCLC

At present,a number of immunocheckpoint inhibitors have been approved for the treatment of non-small cell lung cancer(NSCLC).Most clinical studies have shown significant differences in the efficacy of immunocheckpoint inhibitors in NSCLC patients with different epidermal growth factor receptor(EGFR)mutation states,and the mechanism is still unclear.In this study,the expression of programmed death-ligand 1(PD-L1)in the primary tumor of NSCLC patients and the infiltration of CD8~+T lymphocytes in immune microenvironment were investigated,and the classification of immune microenvironment was further analyzed:The distribution of CD8~+PD L1~+(type I),and CD8~-PD-L1~-(type II),CD8~-PD-L1~+(type III),and CD8~+PD-L1~-(type IV)in different NSCLC patients and their correlation with EGFR mutation status,providing experimental basis for screening the benefit population of immunotherapy.We included paraffin tissue samples from 74 NSCLC patients admitted to the Air Force Medical Center of characteristics from January2016 to July 2018,and collected their relevant clinicopathological data.All patients received EGFR gene test,and none received radiotherapy,chemotherapy or targeted therapy.The results showed that there were statistically significant differences in PD-L1 expression in primary NSCLC in patients of different genders,pathological types,smoking history,and EGFR gene mutation status(P<0.05).In addition,the expression of PD-L1 in male,squamous cell carcinoma,smoking and EGFR wild-type NSCLC patients was higher than that in female,adenocarcinoma,non-smoking and EGFR mutant patients.The infiltration of CD8~+T lymphocytes in tumor microenvironment showed statistically significant differences in different TNM stage and lymph node metastasis(P<0.05),In other words,CD8~+T cell infiltration in NSCLC patients with advanced and lymph node metastasis was higher than that in patients with early stage and no lymph node metastasis.PD-L1expression in primary tumor of NSCLC patients was significantly correlated with EGFR mutation status(P=0.000),while the infiltration of CD8~+T lymphocytes in tumor microenvironment was not correlated with EGFR mutation status(P=0.605).In this group,CD8~+PD-L1~+(type I)was the most(36.5%)and CD8~-PD-L1~+(type III)was the least(14.8%).Immune microenvironment classification in different EGFR mutation,smoking history,pathological differentiation degree of distribution in each group have significant difference(P<0.05),EGFR mutation and no smoking of smoking of NSCLC patients immune microenvironment in CD8~-PD-L1~-(type II)and CD8~+PD-L1~-(type IV)are more,wild type and NSCLC patients with smoking CD8~+PD-L1~+(type I)more;CD8~+PD-L1~-(type IV)was more common in the immunomicroenvironmental typing of NSCLC patients with moderate to high degree of pathological differentiation,while CD8~+PD-L1~+(type I)was more common in the immunomicroenvironmental typing of NSCLC patients with low degree of pathological differentiation.The immune microenvironment of NSCLC patients was significantly correlated with EGFR gene mutation(P<0.05).Follow-up showed that type I(17/36),type II(11/26)and type I(5/12)were the most common among patients with disease-free survival,recurrence,metastasis and death,respectively.In summary,the expression of PD-L1 in primary tumors of EGFR wild-type NSCLC patients was higher than that of EGFR mutant NSCLC patients.EGFR mutation down-regulated PD-L1 expression,but had no effect on CD8~+T cell infiltration in tumor microenvironment.PD-L1expression was significantly correlated with EGFR mutation,while CD8~+T cell infiltration was not correlated with EGFR mutation.EGFR mutation affects the tumor immune microenvironment of NSCLC patients,which is dominated by CD8~+PD-L1~+(type I)and least by CD8~-PD-L1~+(type III).The immune microenvironment of EGFR mutant NSCLC patients was dominated by CD8~-PD-L1~-(type II)and CD8~+PD-L1~-(type IV),while the immune microenvironment of wild NSCLC patients was dominated by CD8~+PD-L1~+(type I).The survival status of NSCLC patients with different immune microenvironments is significantly different,and the evaluation of the immune microenvironment on the prognosis of NSCLC patients and the efficacy of immune checkpoint inhibitors requires further evaluation by more clinical studies.