“Neutrophils drive vascular occlusion, pleomorphic tumour necrosis, and metastasis”

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• Jose M. Adrover, Francis Crick Institute
• Thursday 20 February 2025, 16:00-17:00
• Lecture Theatre, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus.

If you have a question about this talk, please contact Ruth Paton.

We are delighted to welcome Jose M. Adrover, The Francis Crick Institute as the speaker for this week’s Cambridge Immunology Network Seminar Series.

Talk Title: “Neutrophils drive vascular occlusion, pleomorphic tumour necrosis, and metastasis”

Abstract: Tumour necrosis is associated with poor prognosis in cancer and is thought to occur passively when tumour growth outpaces nutrient supply. We found, however, that neutrophils actively induce tumour necrosis. In multiple cancer mouse models, we found a tumour-elicited Ly6GHigh Ly6CLow neutrophil population that was unable to extravasate in response to inflammatory challenges but formed neutrophil extracellular traps (NETs) more efficiently than classical Ly6GHigh Ly6CHigh neutrophils. The presence of these “vascular restricted” neutrophils correlated with the appearance of a “pleomorphic” necrotic architecture in mice. In tumours with pleomorphic necrosis, we found intravascular aggregates of neutrophils and NETs that caused occlusion of the tumour vasculature, driving hypoxia and necrosis of downstream vascular beds. Furthermore, we found that cancer cells adjacent to these necrotic regions (i.e., in “peri-necrotic” areas) underwent epithelial-to-mesenchymal transition, explaining the paradoxical metastasis-enhancing effect of tumour necrosis. Blocking NET formation genetically or pharmacologically reduced the extent of tumour necrosis and lung metastasis. Thus, by showing that NETs drive vascular occlusion, pleomorphic necrosis, and metastasis, we critically demonstrate that tumour necrosis is not necessarily a passive byproduct of tumour growth and that it can be blocked to reduce metastatic spread.

Date: Thursday, 20 February 2025

Time: 16:00-17:00 GMT

Location: Ground Floor Lecture Theatre, Jeffrey Cheah Biomedical Centre (JCBC)

Host: Maike De La Roche, Cancer Research UK Cambridge Institute

We encourage in-person attendance. However, if you are unable to join us, please email enquiries@immunology for a Zoom link.

Refreshments are provided following the seminar for attendees.

The seminar series is a collaboration between the Cambridge Immunology Network and supported by the Cambridge Institute of Translational Immunology and Infectious Disease (CITIID).

Seminars take place weekly on Thursdays at 4pm and feature a leading speaker from the immunology field.

For more information please contact: enquiries@immunology.ac.uk

This talk is part of the Cambridge Immunology Network Seminar Series series.

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