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Integrin-dependent neutrophil slowing reduces lung perfusion and supports metastasis in a model of breast cancer

Neutrophils are critical in establishing a tumor-cell-nurturing and immunosuppressive pulmonary “pre-metastatic” niche in breast cancer. The localization and behavior of these neutrophils is, however, not well described. Using multiplexed imaging to investigate the pre-metastatic lung in a spontaneo...

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Autori principali: Fercoq, Frédéric (Autore) , Cairns, Gemma S. (Autore) , Bridgeman, Victoria L. (Autore) , De Donatis, Marco (Autore) , Mackey, John B. G. (Autore) , Floerchinger, Alessia (Autore) , McFarlane, Amanda J. (Autore) , Secklehner, Judith (Autore) , Raffo-Iraolagoitia, Ximena L. (Autore) , Harrington, Madeline (Autore) , McGarry, Lynn (Autore) , Brownlie, Demi (Autore) , Whyte, Declan (Autore) , Arnott, Lindsey W. G. (Autore) , Nixon, Colin (Autore) , Wiesheu, Robert (Autore) , Kilbey, Anna (Autore) , Brown, Leah (Autore) , Al-Khalidi, Sarwah (Autore) , Norman, Jim C. (Autore) , Roberts, Edward W. (Autore) , Malanchi, Ilaria (Autore) , Blyth, Karen (Autore) , Coffelt, Seth B. (Autore) , Carlin, Leo M. (Autore)
Natura: Article (Journal)
Lingua:inglese
Pubblicazione: 24 March 2026
In: Cell reports
Year: 2026, Volume: 45, Fascicolo: 3, Pages: 1-20
ISSN:2211-1247
DOI:10.1016/j.celrep.2026.117101
Accesso online:Resolving-System, kostenfrei, Volltext: https://doi.org/10.1016/j.celrep.2026.117101
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2211124726001798
Testo
Note sull'autore:Frédéric Fercoq, Gemma S. Cairns, Victoria L. Bridgeman, Marco De Donatis, John B. G. Mackey, Alessia Floerchinger, Amanda J. McFarlane, Judith Secklehner, Ximena L. Raffo-Iraolagoitia, Madeline Harrington, Lynn McGarry, Demi Brownlie, Declan Whyte, Lindsey W. G. Arnott, Colin Nixon, Robert Wiesheu, Anna Kilbey, Leah Brown, Sarwah Al-Khalidi, Jim C. Norman, Edward W. Roberts, Ilaria Malanchi, Karen Blyth, Seth B. Coffelt, and Leo M. Carlin
Descrizione
Riassunto:Neutrophils are critical in establishing a tumor-cell-nurturing and immunosuppressive pulmonary “pre-metastatic” niche in breast cancer. The localization and behavior of these neutrophils is, however, not well described. Using multiplexed imaging to investigate the pre-metastatic lung in a spontaneously metastatic mammary cancer model, we uncover that neutrophils with impaired intravascular motility congest the capillaries of pre-metastatic lungs. Slowed neutrophil transit is reversed by activating β2 integrin with an antibody and can be recapitulated by treating non-tumor-bearing mice with G-CSF. Neutrophil congestion causes a reduction of intravenously injected microbeads in the lung, suggestive of lower perfusion. In a model where tumor cells are injected intravenously into mammary-cancer-bearing Rag1-deficient mice, we observe lower lung experimental metastasis burdens after activating β2 integrins. Overall, our study proposes that integrin-mediated neutrophil congestion of the alveolar capillaries contributes to the pulmonary pre-metastatic niche.
Descrizione del documento:Online veröffentlicht am: 15. März 2026
Gesehen am 31.07.2026
Descrizione fisica:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2026.117101

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