Thank you!

We want to thank all our collaborators, editors, reviewers and the funding agencies @erc.europa.eu #ISF #ICRF for their contribution and support in the study. www.nature.com/articles/s43...

To sum up: we uncovered a complex signaling niche driving a more aggressive TME: macrophages recruit neutrophils which physically interact with tumor cells (PICs) inducing proliferation & invasion as well as angiogenesis through PICs-vasculature crosstalk.

Finally, we showed the causality between neutrophil-cancer cell physical crosstalk and tumor cell proliferation and invasion properties. Specifically, in vivo neutrophil depletion during advanced-stage breast cancer resulted in reduced endothelial and epithelial proliferation.

We were fascinated to find that the physical interaction between neutrophils and tumor cells also induces a pro-tumoral gene program of proliferation and invasion, which significantly correlates with worse survival in advanced stage #breastcancer patients.

By integrating ligand-receptor and PIC-seq analyses with functional experiments, we found that neutrophils are recruited to the tumor niche mainly by tumor-activated macrophages, and then send pro-angiogenic signals to the perivascular niche.

In-depth molecular characterization of #neutrophils in the mammary gland revealed highly dynamic states. Importantly, tumor-associated neutrophil states expressed a gene signature setting them apart from blood-circulating neutrophils that was shared across primary tumor sites.

As immune and epithelial cell states were highlighted in the tumor niche, we applied PIC-seq, to molecularly investigate their physical interactions. Surprisingly, we found a significant enrichment of neutrophils in physical crosstalk with tumor cells during advanced carcinoma.

After seeing differences in tissue composition during development, normal adulthood and cancer, we defined cellular niches related to each stage by grouping cell states with similar trends in abundance over time. This allowed us to focus our attention on the tumor niche.

We started by exploring immune/non-immune crosstalk during mammary gland development and cancer to unveil tumor-specific cellular states & interactions. To achieve this, we used the MMTV-PyMT mouse model and performed scRNA-seq and PIC-seq.