Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality.

IF 6.5 2区医学 Q1 ONCOLOGY

NPJ Breast Cancer Pub Date : 2025-01-23 DOI:10.1038/s41523-025-00721-2

Noor A M Bakker, Hannah Garner, Ewald van Dyk, Elisa Champanhet, Chris Klaver, Maxime Duijst, Leonie Voorwerk, Iris Nederlof, Rosie Voorthuis, Marte C Liefaard, Marja Nieuwland, Iris de Rink, Onno B Bleijerveld, Hendrika M Oosterkamp, Lodewyk F A Wessels, Marleen Kok, Karin E de Visser

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引用次数: 0

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. Vδ1 γδ T cells from mTNBC patients produced more IL17 than those from HDs. Chemotherapy-naïve 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.

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来源期刊

NPJ Breast Cancer Medicine-Pharmacology (medical)

CiteScore

10.10

自引率

1.70%

发文量

122

审稿时长

9 weeks

期刊介绍： npj Breast Cancer publishes original research articles, reviews, brief correspondence, meeting reports, editorial summaries and hypothesis generating observations which could be unexplained or preliminary findings from experiments, novel ideas, or the framing of new questions that need to be solved. Featured topics of the journal include imaging, immunotherapy, molecular classification of disease, mechanism-based therapies largely targeting signal transduction pathways, carcinogenesis including hereditary susceptibility and molecular epidemiology, survivorship issues including long-term toxicities of treatment and secondary neoplasm occurrence, the biophysics of cancer, mechanisms of metastasis and their perturbation, and studies of the tumor microenvironment.