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

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

doi:10.1038/s41523-025-00721-2

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

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^*

^*Corresponding author for this work

Netherlands Cancer Institute
Oncode Institute
Leiden University
Groene Hart Hospital
Haaglanden Medisch Centrum

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	5
Journal	npj Breast Cancer
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41523-025-00721-2
Publication status	Published - 1 Dec 2025

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Triple-negative-breast-cancer-modifies-the-systemic-immune-landscape-and-alters-neutrophil-functionality.pdfFinal published version, 2.41 MBLicence: CC BY

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Bakker, N. A. M., Garner, H., van Dyk, E., Champanhet, E., Klaver, C., Duijst, M., Voorwerk, L., Nederlof, I., Voorthuis, R., Liefaard, M. C., Nieuwland, M., de Rink, I., Bleijerveld, O. B., Oosterkamp, H. M., Wessels, L. F. A., Kok, M., & de Visser, K. E. (2025). Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality. npj Breast Cancer, 11(1), Article 5. https://doi.org/10.1038/s41523-025-00721-2

@article{74b87656f3a849a1b3a5279db66d7436,

title = "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. Vδ1 γδ T cells from mTNBC patients produced more IL17 than those from HDs. Chemotherapy-na{\"i}ve 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.",

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

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = dec,

day = "1",

doi = "10.1038/s41523-025-00721-2",

language = "English",

volume = "11",

journal = "npj Breast Cancer",

issn = "2374-4677",

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}

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 2025, 'Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality', npj Breast Cancer, vol. 11, no. 1, 5. https://doi.org/10.1038/s41523-025-00721-2

TY - JOUR

T1 - Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality

AU - Bakker, Noor A. M.

AU - Garner, Hannah

AU - van Dyk, Ewald

AU - Champanhet, Elisa

AU - Klaver, Chris

AU - Duijst, Maxime

AU - Voorwerk, Leonie

AU - Nederlof, Iris

AU - Voorthuis, Rosie

AU - Liefaard, Marte C.

AU - Nieuwland, Marja

AU - de Rink, Iris

AU - Bleijerveld, Onno B.

AU - Oosterkamp, Hendrika M.

AU - Wessels, Lodewyk F. A.

AU - Kok, Marleen

AU - de Visser, Karin E.

PY - 2025/12/1

Y1 - 2025/12/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85218131551

U2 - 10.1038/s41523-025-00721-2

DO - 10.1038/s41523-025-00721-2

M3 - Article

C2 - 39843922

SN - 2374-4677

VL - 11

JO - npj Breast Cancer

JF - npj Breast Cancer

IS - 1

M1 - 5

ER -

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

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