The Investigation Of Relationship Between Tumor-infiltrating Lymphocytes Expressed CD8 And FOXP3 In Triple-negative Breast Carcinoma And Its Clinical Pathological Characteristics And Tumor Prognosis

[Objective]Tumor immune microenvironment plays an important part of the occurrence,development,metastasisand proliferationof tumor.In this study,we detect the percentage of stromal Tumor-infiltrating lymphocytes(sTILs)and the intensity of CD8 or FOXP3 positive lymphocytes in triple-negative breast cancer,in order to analyze their correlation with clinicopathological features,and to explore their meaning in TNBC tumor prognosis.[Materials and Methods]Histopathologic analysis of the percentage of sTILs was performed on hematoxylin and eosin-stained sections,and MaxVision immunohistochemistry method was used for detecting the intensity,distribution and ratio of CD8 and FOXP3.All 160 triple-negative breast carcinoma cases from the surgical excision or biopsy specimens without chemotherapy and radiotherapy were included in this study.Statistical analysis was proceed to detect the relationship between the result and followed-up information such as clinicopathologic features,recurrence,prognosis.[Results]1.Infiltrating lymphocytes in tumor microenvironment of breast carcinoma presented in following patterns.The lymphocytes infiltrating within the boundaries of tumor infiltration included intratumor TILs(iTILs)and stromal TILs(sTILs).iTILs presented in a diffuse pattern,and directly contacted with tumor cells.sTILs presented in stroma within the boundaries of tumor infiltration,and indirectly contacted with tumor cells,including lymphocytes infiltrating in the border zone,those were more abundant and intended to form lymphoid aggregates.There were some other tumor-infiltrating lymphocytes,which stayed outside the boundaries of tumor infiltration,usually forming lymphoid aggregates even lymphoid follicle structure,namely Tertiary lymphoid structures(TLS).2.In TNBC,the percentage of sTILs was positively correlated with Ki67(rs=0.237,P=0.002).3.In stroma,the density of CD8+ lymphocytes was negatively correlated with tumor size(rs=-O.214,P=0.009)and positively correlated with Ki67(rs=0.188,P=0.021).The density of FOXP3 + lymphocytes was inversely correlated with patient age(rs=-O.179,P=0.030)and positively correlated with histological grade(rs=0.184,P=0.026).The percentage of sTILs was positively correlated with the density of stromal CD8+ lymphocytes(rs=0.200,P=0.014).4.Within tumor bed,the density of CD8+ lymphocytes was positively correlated with Ki67(rs=0.184,P=0.026).5.Univariate analyses showed:The high percentage of sTILs was found to be significantly associated with improved overall survival(OS)and progression-free survival(PFS)(OS,P=0.001;PFS,P=0.033).The high CD8’/FOXP3+ ratio was found to be significantly associated with improved overall survival(OS)(P=0.040).Patient age was positively correlated with progression-free survival(PFS)(P=0.044).Tumor size was negatively correlated with overall survival(OS)and progression-free survival(PFS)(OS,P=0.016;PFS,P=0.014).6.Multivariate Cox regression prognosis analyses showed:The percentage of sTILs and patient age were positively correlated with progression-free survival(PFS)P=0.029,P=0.043).Tumor size was negatively correlated with progression-free survival(PFS)(P=0.046).The percentage of sTILs was an Independent prognostic factor for progression-free survival(PFS)of TNBC.[Conclusions]The impact of Tumor infiltrating lymphocytes on the tumor prognosis depends on the types of infiltrating cells,functional status,position of infiltrating cells in tumor tissue,and the interaction of tumor cells.The percentage of stromal TILs and the density of CD8+ lymphocytes were associated with the proliferation of triple-negative breast cancers.Stromal TILs were positively correlated with the density of stromal CD8+ lymphocytes.sTILs was an independent prognostic factor for progression-free survival(PFS)of TNBC.Tumor-infiltrating lymphocytes will be a promising evaluation index of histomorphology in breast cancer,and may provide a potential target for clinicopathologic diagnosis and adjuvant therapy in TNBC.