Bakker Noor A M, Garner Hannah, van Dyk Ewald, Champanhet Elisa, Klaver Chris, Duijst Maxime, Voorwerk Leonie, Nederlof Iris, Voorthuis Rosie, Liefaard Marte C, Nieuwland Marja, de Rink Iris, Bleijerveld Onno B, Oosterkamp Hendrika M, Wessels Lodewyk F A, Kok Marleen, de Visser Karin E
Division of Tumor Biology & Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Oncode Institute, Utrecht, The Netherlands.
NPJ Breast Cancer. 2025 Jan 23;11(1):5. doi: 10.1038/s41523-025-00721-2.
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.
癌症会破坏肿瘤内先天性免疫与适应性免疫的相互作用，但在乳腺癌进展过程中全身免疫格局如何演变仍不清楚。我们对I-III期和IV期三阴性乳腺癌（TNBC）患者以及健康供体（HD）的循环免疫细胞进行了分析。与非转移性TNBC患者和HD相比，转移性TNBC（mTNBC）患者的T细胞、树突状细胞和分化B细胞减少，部分与先前的化疗有关。mTNBC患者的Vδ1 γδ T细胞比HD的产生更多的IL17。未接受过化疗的mTNBC患者表现出经典单核细胞和中性粒细胞增加。转录组、蛋白质组和功能分析表明，mTNBC中的中性粒细胞表现出增强的迁移能力、升高的颗粒蛋白和更高的活性氧产生。一些免疫变化，如未转换B细胞减少和中性粒细胞迁移增强，在早期TNBC阶段就很明显。这项研究全面描绘了TNBC中的全身免疫情况，为未来患者分层和免疫调节策略的研究提供了指导。
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