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

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 (IL1 beta) 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, IL1 beta or CCL2 may reduce TAM recruitment and resistance to ICI, illuminating the potential of combination immunotherapy in TNBC.

Automated summary

Compared with other breast cancer subtypes, triple negative breast cancer (TNBC) is more aggressive and has a higher recurrence rate and lower overall survival. Notch signaling drives the expression of IL1 beta and CCL2 in TNBC, resulting in the recruitment of TAMs and immune evasion. Targeting Notch, IL1 beta, or CCL2 may reduce TAM recruitment and resistance to ICIs, suggesting the potential of combination immunotherapy in TNBC.