NF-κB associated markers of prognosis in early and metastatic triple negative breast cancer

Abstract

Abstract Background Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. While PD-1 based immunotherapies overall have led to improved treatment outcomes for this disease, a diverse response to frontline chemotherapy and immunotherapy still exist in TNBC, highlighting the need for more robust prognostic markers. Methods Tumor-intrinsic immunotranscriptomics, serum cytokine profiling, and tumor burden studies were conducted in two syngeneic mouse models to assess differential effects in both the early-stage and metastatic setting. Bioinformatic analyses of both early and metastatic TNBC patient data were performed to assess if identified NF-κB-associated factors are associated with improved patient clinical outcomes. Results NF-κB signaling driven by lymphotoxin beta expression is associated with tumor regression in TNBC mouse models. Furthermore, lymphotoxin beta expression in patient TNBC cohorts is prognostic of improved survival outcomes. Conclusions This study highlights the potential role for NF-κB-associated factors, specifically lymphotoxin beta to be used as prognostic markers in TNBC, which could ultimately provide insight for improved targeted treatment approaches in the clinic.

Keywords

• Triple negative breast cancer
• Immunotherapy
• Immune checkpoint inhibitors
• Biomarkers
• NF-κB pathway