The Clinicopathological Significance Of PTEN,STING、IRF3 And PD1+ Tumor Infiltration Lymphocytes In Triple Negative Breast Cancer

Object:This study aims to study the prognostic features and relationships of PTEN,STING,IRF3,the expression of TIL and PD1+ tumor infiltration lymphocytes(TILPD1)in triple negative breast cancer(TNBC),and their influence on prognosis,which provide some help for exploring the relevant mechanism of tumor Immune microenvironment of TNBC,improving the specificity of tumor checkpoint blockade(ICB)therapy,and improving the good prognosis of patients.Methods:Specimens of 76 TNBC patients and 46 other types(NTNBC)were collected in the first affiliated hospital of Bengbu Medical College.These specimens were then immunohistochemically evaluated for expression of PTEN,STING,IRF3 and TILPD1.Clinicopathological characters,and prognostic features were statistical analyzed.This experiment explored the expression and role of PTEN in TNBC,the correlation between the related immune response and TBK1/IKK innate immune pathway markers STING/IRF3,and the regulation of PTEN/STING/IRF3 for downstream T cell exhaustion represented by TILPD1.Results:Higher degree of tumor infiltrating lymphocytes and STING/IRF3 expression was found in TNBC groups.In TNBC tissues,PTEN was negatively correlated with STING/IRF3 and TILPD1 expression,STING/IRF3 was positively correlated with TILPD1 expression,and TILPD1 expression was significantly positively correlated with tumor stromal TIL infiltration(P=0.012,0.031,0.019,0.035).PTEN was negatively correlated with the clinical stage of tumor(P=0.002),and was also correlated with TIL infiltration,tumor metastasis rate and histological grade.Univariate and multivariate survival analyses showed that those patients with lower TNM grade,no lymph node or distant metastasis had better clinical prognosis,while PTEN deficiency and TILPD1 high expression were independent risk factors with TNBC.Conclusions:In this study,we investigated the expressions of PTEN,STING,IRF3 and TILPD1 proteins in TNBC and the differences between them and the control group,and analyzed their correlation with the clinicopathological characteristics and prognosis of the patients.The absence of PTEN and the high expression of TILPD1 are independent risk factors for survival and prognosis in TNBC patients.TILPD1 level in tumor microenvironment is regulated by PTEN gene,and there is a complex equilibrium relationship with TBK1/IKK innate immune pathway markers STING/IRF3,the related mechanism needs to be further explored.This topic at the protein level of PTEN protein in TNBC discussed by STING/IRF3 pathways for the regulation of T cells in tumor microenvironment exhaustion.Related mechanism,as well as the correlation of TILPD1 high expression and anti-PD1/PDL1 combination therapy in clinical prospective,need study further found.