From guardians to foes: Host remodelling and neutrophil plasticity in cancer

 Host

Ana Luísa Correia, PhD, Cancer Dormancy & Immunity Lab

Venue

Seminar Room

Abstract

Tumour necrosis is associated with poor prognosis in cancer. It is generally considered a passive process that occurs when tumour growth outpaces nutrient supply. But we recently found that tumour necrosis can also be reframed as an active, neutrophil-driven vascular process. We identified a cancer-elicited subpopulation of neutrophils that expands during cancer-associated hematopoietic remodelling, which does not extravasate in response to inflammatory stimuli. These “vascular-restricted neutrophils” (vrPMNs) are also prone to neutrophil extracellular trap formation and interact more with platelets compared to conventional neutrophils. In tumours, neutrophils form intravascular aggregates that occlude vessels, disrupt perfusion, and induce a distinct pleomorphic necrosis architecture observed in murine breast and lung cancer models and human triple-negative breast cancer. Genetic or pharmacologic inhibition of NET formation reduces vascular occlusion, limits necrosis, and decreases metastatic spread. This reduction in metastasis correlated with a decrease in the area of peri-necrotic tissue, where cancer cells became more metastasis proficient. We thus propose that tumour necrosis is not necessarily a passive phenomenon arising as a byproduct of tumour growth and that it can be blocked to reduce metastatic spread. Ongoing work in the lab suggests that vrPMNs also act systemically, linking malignancy to cancer-elicited cardiovascular disease through their pro-thrombotic intravascular activity. Thus, cancer-elicited changes to neutrophil biology may provide a mechanistic explanation for the disproportionately high rates of adverse cardiovascular events that cancer patients endure. Furthermore, our recent findings suggest that cancer drives an oncofoetal reversion of haematopoiesis, which reactivates developmental programs that generate vrPMNs. Overall, we propose that vrPMNs are a cancer-induced reversion to a developmentally programmed neutrophil state that links tumour necrosis, metastatic progression, and cardiovascular comorbidities, revealing a therapeutically tractable axis for limiting both tumour-specific and systemic consequences of cancer.

Bio

Jose M. Adrover, PhD, is a Group Leader at the Francis Crick Institute in London, where he leads the Cancer Macroenvironment Laboratory. His research focuses on neutrophil biology and the systemic interactions between cancer and the host, with particular emphasis on how altered granulopoiesis, neutrophil states and neutrophil extracellular traps influence tumour progression and metastasis. He trained in Andrés Hidalgo’s laboratory at CNIC, where he completed his PhD studying neutrophil homeostasis and inflammation, before undertaking postdoctoral research with Mikala Egeblad at Cold Spring Harbor Laboratory and Johns Hopkins University. His work has contributed to understanding neutrophil ageing, trafficking and function in inflammation and cancer. He is a recipient of the 2026 Metastasis Research Society Sue Eccles Early Career Investigator Award and serves on the Steering Committee of the AACR Tumor Microenvironment Working Group.

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About CR Colloquia Series

Champalimaud Research (CR) Colloquia Series is a seminar programme organised by the Champalimaud Centre for the Unknown to promote the discussion about the most interesting and significant questions in neuroscience and physiology & cancer with appointed speakers by the CR Community.