Toll-Like Receptor 9 Expression Levels in Breast Carcinoma Correlate with Improved Overall Survival in Patients Treated with Neoadjuvant Chemotherapy and Could Serve as a Prognostic Marker.

Toll-like receptor 9 (TLR9) can recognize the DNA fragments released from chemotherapy-treated cancer cells in tumor tissues and induce an inflammatory response. The aim of the present study was to evaluate the survivability benefit of TLR9 expression levels as a potential prognostic marker in breast cancer patients treated with neoadjuvant chemotherapy (NACT). To study the expression of TLR9 in breast tumor, immunohistochemical (IHC) analyses were performed on two patient cohorts, with NACT ( = 19) and without NACT ( = 23). To corroborate the findings from the in-house cohort, we also used publicly available datasets including SurvExpress (GSE 20685) and the Kaplan-Meier plotter tool (GSE 16446) to analyze the relationship between the expression of TLR9 and overall survivability for NACT. The IHC analyses of our inhouse cohort demonstrated that TLR9 was expressed in both malignant breast epithelial cancer cells as well as in the adjacent stromal cells. The IHC results also indicated that, the percentage of malignant epithelial cells (54.76%) expressing TLR9 was higher than in the adjacent stromal compartment (11.9%). We also observed an increase in the expression levels of TLR9 in the patients who were given NACT ( = 0.0379). Further, the analysis of publicly available datasets demonstrated that elevated TLR9 expression was related to increased overall survival in patients treated with NACT. In this study, we show for the first time that elevated TLR9 tissue expression levels in breast cancer may serve as a prognostic marker for patients treated with NACT and could potentially be used to select the neoadjuvant regime.