Integrin-dependent neutrophil slowing reduces lung perfusion and supports metastasis in a model of breast cancer
Abstract
Neutrophils are thought to be critical to the process whereby breast cancers establish an immunosuppressive and tumour cell nurturing ‘pre-metastatic’ niche before overt metastasis can be detected. However, the spatial localization of neutrophils and their interaction with other cell types in the lung pre-metastatic niche is not well described. We used a spontaneously metastatic mammary cancer model combined with a multiplexed three- and four-dimensional imaging approach to investigate the behaviour of neutrophils in the pre-metastatic niche. Volume fixed tissue three-dimensional imaging showed that approximately 40% of CD8 + T cells are adjacent to neutrophils at this stage. In live tissue, we found neutrophils with impaired intravascular motility congested the capillaries of pre-metastatic lungs potentially obstructing CD8 + T cells. Slowed neutrophil transit was dependent on the conformation of β2-integrin and could be recapitulated by treating non-tumour bearing mice with G-CSF, a potent systemic mediator of granulopoiesis. We found a decrease in L-selectin (CD62L) on neutrophils in the lungs of both mammary tumour bearing and G-CSF treated mice. Finally, we observed differential accumulation of intravenously injected micro-beads in the lung, suggestive of transient circulatory dead spaces which were also dependent on β2-integrin inactivation. Overall, our study proposes that integrin-mediated neutrophil congestion of the alveolar capillaries could contribute to the generation of the pulmonary pre-metastatic niche.
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BibTeX
@article{fercoq2026integrindependent,
title = {{Integrin-dependent neutrophil slowing reduces lung perfusion and supports metastasis in a model of breast cancer}},
author = {Frédéric Fercoq and Gemma Cairns and Victoria Bridgeman and Marco de Donatis and John B.G. Mackey and Alessia Floerchinger and Amanda Mcfarlane and Judith Secklehner and Ximena Raffo-Iraolagoitia and Madeline Harrington and Lynn Mcgarry and Demi Brownlie and Declan Whyte and Lindsey W.G. Arnott and Colin Nixon and Robert Wiesheu and Anna Kilbey and Leah Brown and Sarwah Al-Khalidi and Jim Norman and Edward Roberts and Ilaria Malanchi and Karen Blyth and Seth Coffelt and Leo Carlin},
journal = {Cell Reports},
year = {2026},
month = oct,
doi = {10.1016/j.celrep.2026.117101},
url = {https://hal.science/hal-05794263v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Integrin-dependent neutrophil slowing reduces lung perfusion and supports metastasis in a model of breast cancer
AU - Frédéric Fercoq
AU - Gemma Cairns
AU - Victoria Bridgeman
AU - Marco de Donatis
AU - John B.G. Mackey
AU - Alessia Floerchinger
AU - Amanda Mcfarlane
AU - Judith Secklehner
AU - Ximena Raffo-Iraolagoitia
AU - Madeline Harrington
AU - Lynn Mcgarry
AU - Demi Brownlie
AU - Declan Whyte
AU - Lindsey W.G. Arnott
AU - Colin Nixon
AU - Robert Wiesheu
AU - Anna Kilbey
AU - Leah Brown
AU - Sarwah Al-Khalidi
AU - Jim Norman
AU - Edward Roberts
AU - Ilaria Malanchi
AU - Karen Blyth
AU - Seth Coffelt
AU - Leo Carlin
PY - 2026
DA - 2026/10/12
JO - Cell Reports
DO - 10.1016/j.celrep.2026.117101
UR - https://hal.science/hal-05794263v1
AB - Neutrophils are thought to be critical to the process whereby breast cancers establish an immunosuppressive and tumour cell nurturing ‘pre-metastatic’ niche before overt metastasis can be detected. However, the spatial localization of neutrophils and their interaction with other cell types in the lung pre-metastatic niche is not well described. We used a spontaneously metastatic mammary cancer model combined with a multiplexed three- and four-dimensional imaging approach to investigate the behaviour of neutrophils in the pre-metastatic niche. Volume fixed tissue three-dimensional imaging showed that approximately 40% of CD8 + T cells are adjacent to neutrophils at this stage. In live tissue, we found neutrophils with impaired intravascular motility congested the capillaries of pre-metastatic lungs potentially obstructing CD8 + T cells. Slowed neutrophil transit was dependent on the conformation of β2-integrin and could be recapitulated by treating non-tumour bearing mice with G-CSF, a potent systemic mediator of granulopoiesis. We found a decrease in L-selectin (CD62L) on neutrophils in the lungs of both mammary tumour bearing and G-CSF treated mice. Finally, we observed differential accumulation of intravenously injected micro-beads in the lung, suggestive of transient circulatory dead spaces which were also dependent on β2-integrin inactivation. Overall, our study proposes that integrin-mediated neutrophil congestion of the alveolar capillaries could contribute to the generation of the pulmonary pre-metastatic niche.
SN - 2211-1247
SN - 2211-1247
ER -