Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality.
Abstract
Cancer disrupts intratumoral innate-adaptive immune crosstalk, but how the systemic immune landscape evolves during breast cancer progression remains unclear. We profiled circulating immune cells in stage I-III and stage IV triple-negative breast cancer (TNBC) patients and healthy donors (HDs). Metastatic TNBC (mTNBC) patients had reduced T cells, dendritic cells, and differentiated B cells compared to non-metastatic TNBC patients and HDs, partly linked to prior chemotherapy. Vdelta1 gammadelta T cells from mTNBC patients produced more IL17 than those from HDs. Chemotherapy-naive mTNBC patients showed increased classical monocytes and neutrophils. Transcriptional, proteomic, and functional analyses revealed that neutrophils in mTNBC exhibited enhanced migratory capacity, elevated granule proteins, and higher ROS production. Some immune changes, such as reduced non-switched B cells and heightened neutrophil migration, were evident in earlier TNBC stages. This study comprehensively maps systemic immunity in TNBC, guiding future research on patient stratification and immunomodulation strategies.
| Authors: | Bakker NAM, Garner H, van Dyk E, Champanhet E, Klaver C, Duijst M, Voorwerk L, Nederlof I, Voorthuis R, Liefaard MC, Nieuwland M, de Rink I, Bleijerveld OB, Oosterkamp HM, Wessels LFA, Kok M, de Visser KE, |
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| Journal: | NPJ Breast Cancer;2025Jan23; 11 (1) 5. doi:10.1038/s41523-025-00721-2 |
| Year: | 2025 |
| PubMed: | PMID: 39843922 (Go to PubMed) |