We show, therefore, that tumour necrosis is not a passive phenomenon, but an active phenomenon that we can target by targeting neutrophils or their NET formation ability. And by reducing tumour necrosis we can reduce metastatic spread. (12/13)

There, they form NETs and enter a feedforward loop with platelets that ultimately leads to the blockage of blood flow and subsequent necrosis of downstream tumour regions. This induces cancer cells around these necrotic regions to change and become more metastatic. (11/13)

These neutrophils form NETs more efficiently than normal neutrophils, interact more with platelets, and, intriguingly, cannot extravasate and are stuck in the vasculature. We called them vascular-restricted neutrophils (vrPMNs). (9/13)

Using spatial transcriptomics, we found that tumour necrosis increased metastasis because cancer cells in peri-necrotic areas gained pro-metastatic traits in a TGFb-driven manner. (7/13)

We found that the process was driven by NETs. When we block NETs genetically or pharmacologically, tumour necrosis is greatly reduced. This, interestingly, also reduced metastatic spread. (6/13)

These aggregates were blocking blood flow in the tumour, and that caused the necrosis of downstream tumour regions. (5/13)

Interestingly, around necrotic regions we found vessels that contained intraluminal aggregates of neutrophils, NETs and platelets. (4/13)

We found that the architecture of necrosis was peculiar and intricate in different tumour models (we call it “pleomorphic necrosis”), and these regions were covered by neutrophils and NETs. (3/13)

I had a wonderful time in the Tumor Microenvironment Working Group session! #AACR25 Thanks everyone for the warm welcome and lively discussion!

I’m thrilled to be presenting our work next Monday the 28th at the #AACR25 in beautiful Chicago!