High PD-L1 Expression In Triple Negative Breast Cancer Patients Is Associated With Tumor-infiltrating Lymphocytes And Clinical Outcomes

BackgroundThe 2015 ACS cancer statistics released by Breast Cancer Account of United States shows that the incidence of breast cancer among women (25%) was the first primary of the total incidence of cancer in Unites States. Particularly, the mortality of female breast cancer was 40,000, which accounts for 15%of the total deaths rate’.By comparing with 2008, the World Cancer Statistics in 2012 shows that the mortality Chinese breast cancer has dramatically increased from 48,000 to 697,0002. Despite progress in increasing the means of treatment for breast cancer, but distant metastasis or recurrence in a decade have occurred to more than 50%patients with invasive breast cancer Resulting in treatment failure3. With a 5-year survival for ’triple-negative breast cancer’(TNBC) is only 60%4.consequently, it is essential to introduce a innovative treatment approach to the specific patient group..PD-LI is Programmed death receptor 1 (Programmed death 1, PD-1) the main ligand,PD-Ll is found by Ishida etc in the apoptosis research of T cell hybridoma cell apoptosis related proteins5, In 1999 PD-Ll ligands has been found by Dong and named PD-LI, then named CD27456; Further study found that PD-L2, named CD2737. PD-1:PD-LI signaling pathways can suppress the negative regulation of T cell immune response, and then the immune tolerance, microbial infection and tumor immune escape, allergy plays an important role.It has been approved that there is a association between tumor-infiltrating lymphocytes (TILs) express and high PD-Ll expression in various cancer9-11,13,14. Researchers found cTLA4 expression is associated with breast cancer development,PD-L1+TILs are also with prognosis 15.With the advances in immun-targrting drugs have been approved for use in lung cancer and melanoma clinical applications16,17,However, PD-Ll expression and prevalence of tumor TILs in Chinese TNBC patients remains unclear.only very limited data have been reported to date on the expression of PD-L1 in Chinese TNBC patients.This study aimed to search for a relationship among the expression level of PD-Ll,TILs and clinical manifestations in Chinese patients with triple negative breast cancer particularly on the aspects of prognostic value.ObjectiveTNBC patients has poor prognosis.consequently, it is essential to introduce a innovative treatment approach to the specific patient group, so presumably blocking PD-1:PD-L1 pathways can increase T-cell immune response against tumor activity and enhance anti-tumor immune response of the host. Anti-PD-1 and anti-PD-Ll antibodies have significant antitumor activity in the experiments 12, and PD-L1, however at present in TNBC clinical studies and analysis data insufficient.StatisticsAll statistical analyses were performed using SPSS statistics software version 19.Kaplan-Meier survival curves were generated to examine the relationship between the expression levels of PD-L1 and patients’survival rate. Overall survival (OS) was calculated from the date of tumor diagnosis to death from any cause, or time of the last visit. The primary endpoint for this analysis was disease-free survival (DFS), which is defined as the length of time from the date of tumor diagnosis to local, regional, or distant recurrence or to death from any cause.The statistical significance between two groups was determined using chi-square test, or two-sample t-test as appropriate.The statistical significance is described in figures and in legends, significance was set at a p-value of 0.05.ResultsThe median follow-up time was 67.7 months(range,7-159 months).. Median survival time for patients with positive PD-L189 months, PD-L1-negative patients with median overall survival was 72 months, P=0.019,P<0.05, was statistically significant, median disease-free survival time for patients with positive PD-L1137 months PD-L1-negative patients median disease-free survival time was 116 months,P=0.046, P<0.05, was statistically significant. PD-Ll-postive breast cancer patients had significantly longer disease-free survival (DFS) and Overall survival (OS) than those of PD-L1-negative patients in TNBCSTILs high expression patients of the median survival time was 107 months, STILs expression patients in the median survival time was 82 months, STILs median overall survival for patients with low expression of 64 months, P=0.026,P＜0.05, was statistically significant. STILs high median disease-free survival for patients with 126 months, STILs expression of moderate median disease-free survival for patients with 135 months,STILs low median disease-free survival time was 119 months, P=0.325,P ≥0.05, no statistical significance. The presence of increased stroma lymphocytic infiltrates(STILs) was significantly associated with overall survival (P=0.026).Univariate Cox proportional hazards model analysis showed that PD-L1 and STILs were an independent prognostic factor for tumor prognosis.PD-L1 protein expression was significantly relationship with the presence of elevated STILs. Cases with elevated STILs showed significantly higher expression levels of PD-L1 (P= 0.004).Conclutionour study found that high levels of PD-L1 are expressed in TNBC, which is correlated with the prevalence of TILs. PD-Ll-postive and STILs expression of moderate breast cancer patients had significantly longer disease-free survival (DFS) and Overall survival (OS) than those of PD-L1-negative and STILs expression of low patients in TNBC.