Study On The Relationship Between The Expression Of PD-L1 And The Tumor Infiltrating Immune Cells And The Efficacy Of Chemotherapy In Patients With Breast Cancer Before And After Neoadjuvant Chemotherapy

Objective: The expression of the programmed death ligand 1(PD-L1,Programmed death-ligand-1)and the infiltrating immune cells in tumor microenvironment were detected.The relationship of PD-L1 with clinicopathological features of breast cance were analyzed.The relationship of the expression of PD-L1 and the infiltration of immune cells with the effect of neoadjuvant chemotherapy in breast cancer were explored.Method:95 cases of breast invasive ductal carcinoma treated with neoadjuvant chemotherapy between January 2014-June 2016 were collected.At the same time,30 cases of breast fibroadenoma and normal breast tissues were collected.Every patient materials of the Color Doppler ultrasound,mammography,MRI,CT and whole body bone imaging were collected.According to the clinical and pathological data,we evaluated patient with different clinical staging.TAC as neoadjuvant chemotherapy for breast cancer were choosed(cyclophosphamide 500mg/m2,pirarubicin50mg/m2,docetaxel 75mg/m2,21 days for a chemotherapy cycle).The efficacy of chemotherapy after2-3cycles,patients with clinical complete remission,partial remission or no progression after 2-3 cycles of chemotherapy were treated surgically;Immunohistochemistry was used todetect PD-L1,CD8 and CD68 in tumor tissues before and after neoadjuvant chemotherapy.The relationship between the expression of PD-L1 and the clinicopathological features of patients and the relation between PD-L1,CD8+T cells,CD68+ macrophages and the efficacy of neoadjuvant chemotherapy were analyzed.SPSS17.0 statistical software was used to analyze the data,the count data were analyzed by chi square test,and Spearman correlation was used to analyze the correlation of categorical variables.Multivariate analysis was performed by using Logistic regression.Results:1.The expression of PD-L1 in normal breast tissue were detected,and in breast fibroadenoma was not expression or weak expression.The expression of PD-L1 in breast cancer was significantly higher than that in normal breast tissues and fibroadenoma(P<0.05).2.The expression of PD-L1 in breast cancer was not correlated with age and histological grade(P >0.05),but the tumor size,ER,PR,Her2,lymph node metastasis were significantly correlated,the difference was statistically significant(P<0.05).The positive expression of PD-L1 is higher in late stage of T and N.And higher PD-L1 in ER,PR,Her2 negative expression tumour.3.The efficacy of chemotherapy with TAC was not correlated with age,clinical stage,histological grade,molecular type and ER expression(P > 0.05),but the expression of PR and Her2 were significantly correlated(P<0.05).The efficacy of chemotherapy with TAC were correlated with PR and Her2 negative patients.4.The expression of PD-L1 and the variation of PD-L1before and after chemotherapy were correlated with the efficacy of chemotherapy.CD8+T cells in tumor tissue and its degree of infiltration before and after chemotherapy was also correlated with the efficacy of chemotherapy,and the difference was statistically significant(P<0.05).Patients with PD-L1 negative and CD8 positive were in the greater benefit of chemotherapy.However,our results showed that there was no significant correlation between CD68+ macrophages the efficacy of chemotherapy(P>0.05).5.There was a negative correlation between the expression of PD-L1 and the infiltration of CD8+T cells before and after neoadjuvant chemotherapy(r=-0.332,P=0.001),while the degree of CD68+ macrophage infiltration was not significantly correlated with the expression of PD-L1(P>0.05).Conclusion: 1.The positive expression of PD-L1 is increased in invasive carcinoma,and than that in normal breast tissue and fibroadenoma.The expression of T,N,ER,PR and Her2 is significantly correlated with positive expression of PD-L1,the higher expression of PD-L1 are correlated with Tand N,and mainly in ER,PR,and Her2 negative patients.2.There is no significant correlation between the age,clinical stage,histological grade,molecular type,CD68+ macrophage and neoadjuvant chemotherapy in TAC chemotherapy regimen.However,PR,Her2,PD-L1,CD8+T cells are significantly correlated with neoadjuvant chemotherapy.Patients with PD-L1 negative and CD8+T positive cells are more likely to benefit from chemotherapy,the two can be used as an independent factor forthe short-term efficacy of TAC neoadjuvant chemotherapy.3.The expression of PD-L1 in breast cancer is negatively correlated with the infiltration of CD8+T cells,but no significant correlation with CD68+ macrophages.