Targeting Notch-Driven Cytokine Secretion: Novel Therapies for Triple Negative Breast Cancer.

Abstract

Compared with other breast cancer subtypes, triple negative breast cancer (TNBC) is an aggressive malignancy with a high recurrence rate and reduced overall survival. Immune checkpoint inhibition (ICI) has shown modest results in this subgroup, highlighting the need for improved targeted therapeutic options. Notch is a defining feature of TNBC and drives the expression of interleukin-1 beta (IL1β) and C-C motif chemokine ligand 2 (CCL2). These cytokines are involved in the recruitment of tumor-associated macrophages (TAMs) to the tumor, resulting in immune evasion and tumor progression. Targeting Notch, IL1β or CCL2 may reduce TAM recruitment and resistance to ICI, illuminating the potential of combination immunotherapy in TNBC.